			Home About us Contact

G Polymorphism (g + polymorphism)

Distribution by Scientific Domains

Medical Sciences	83%
Life Sciences	16%

Distribution within Medical Sciences

Oncology & Radiotherapy	15%
Allergy & Clinical Immunology	13%
Gastroenterology & Hepatology	9%
Gastroenterology	6%

Selected Abstracts

Combined effect of IL-10 and TGF-,1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitis

ALLERGY, Issue 8 2009
S.-H. Kim
Background:, It has been known that interleukin (IL)-10 promoter polymorphisms at ,1082A/G, ,819T/C and ,592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-,. The goal of this study was to investigate a gene,gene interaction between IL-10 and TGF-,1 polymorphisms in Korean asthmatics with aspirin hypersensitivity. Methods:, Single-nucleotide polymorphism genotyping of IL-10 and TGF-,1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay. Results:, Among the patients with asthma, polymorphism at ,1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, Pc = 0.021). Moreover, a synergistic effect between the TGF-,1,509C/T and IL-10,1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-,1,509C/T and AG or GG genotype of IL-10,1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504,11.235). In an in vitro functional assay, the ,1082G reporter plasmid exhibited significantly greater promoter activity when compared with the ,1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the ,1082G allele. Conclusion:, Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-,1. [source]

The combination of polymorphisms within MCP-1 and IL-1, associated with ulcerative colitis

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2009
K.-S. Li
Summary Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment to sites of inflammation. Raised level of MCP-1 has been widely demonstrated in the intestinal mucosa of patients with ulcerative colitis (UC), suggesting an important role of MCP-1 in the pathogenesis of UC. The ,2518A/G polymorphism in the promoter region of MCP-1 gene affecting its transcriptional activation has been reported recently. In order to assess the potential role of this polymorphism in UC, we examined its distribution in 162 unrelated UC patients and 203 healthy controls. In addition, considering the gene regulatory association between interleukin-1, (IL-1,) and MCP-1, we further examined whether the gene polymorphisms between MCP-1 and IL-1, exert synergetic effects on risk of UC. Our results show that the distribution of MCP-1 genotype or allele frequencies between UC patients and controls was not significantly different; however, the association between the polymorphism of MCP-1 ,2518 GG and the polymorphism of IL-1,,511 T in UC patients is significant (OR 2.062, 95% CI 1.034,4.113, P = 0.038). This is the first report describing the association between MCP-1 polymorphism and UC, and our data suggest that the MCP-1 ,2518 polymorphism itself does not represent an independent genetic risk factor for UC. In contrast, the combination polymorphisms between MCP-1 and IL-1, can increase UC risk significantly, which might help us understand the molecular mechanism underlying the development of UC. [source]

Cytotoxic T lymphocyte associated antigen-4 exon 1 A/G polymorphism in Iranian patients with multiple sclerosis

EUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2008
A. Borhani Haghighi
Background:, Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a T-cell surface receptor of activated T cells. Material and methods:, We studied 100 Iranian patients with clinically definite multiple sclerosis (MS) and 100 ethnic, sex- and age-matched controls. CTLA-4 exon 1 A/G polymorphism was compared amongst patients and controls. Results:, There was no statistically significant difference in the allelic [odds ratio (OR): 1.19, confidence interval (CI) 95%: 0.76,1.85, P = 0.4] and genotypes (OR: 1.60, CI 95%: 0.911,2.824, P = 0.102) distribution amongst patients and controls. Also gender, course and progression index did not reveal any statistically significant differences in allele and genotype distribution of A/G polymorphism. Conclusion:, As a non-European patient population, our results are consistent with the major previous studies showing no significant associations between CTLA4 exon 1 polymorphism and neither MS nor any of its subtypes. [source]

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2000
E. Noguchi
Background IL-4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL-4 gene cluster and asthma and/or asthma-related traits. Interferon regulatory factor 1 (IRF-1) is located approximately 300 kb telomeric to IL-4 and recent study reveals that IRF-1 deficiency results in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of native cell- and Th1-related cytokines. Objective To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5, flanking region of the IRF-1 gene. Methods and results We have screened the promoter and coding regions of the IRF-1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the ,300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF-1 gene. No variants causing amino acid alterations of IRF-1 were detected. The ,300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy- or asthma-affected children. Conclusion The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population. [source]

Surfactant protein A and D gene polymorphisms and protein expression in victims of sudden infant death

ACTA PAEDIATRICA, Issue 1 2009
Arne Stray-Pedersen
Abstract Aim: To investigate the innate immune components surfactant protein A (SP-A) and D (SP-D) in victims of sudden infant death syndrome (SIDS). Methods: Ten common single nucleotide polymorphisms (SNPs) in the exons of SP-A1, SP-A2 and SP-D genes were analysed in 42 cases of SIDS and 46 explained sudden infant deaths. SP-A and SP-D protein expression in tissue from the aerodigestive tract was semi-quantitatively evaluated by immunohistochemistry. Results: SP-D immunoreactivity was found in lungs and tissue from submandibular gland, palatine tonsils and duodenum. Positive SP-A immune staining was found exclusively in lung tissue. Neither the allele nor the haplotype distribution of the SP-A and SP-D genes was significantly different in SIDS compared to explained deaths. The most common SP-A haplotype, 6A2/1A0, tended to be overrepresented in the cases with low immunohistochemical SP-A expression (61%) compared to cases with high expression (49%), p = 0.08. The SP-D expression was not influenced by the 11 C/T or 160 A/G polymorphisms. Conclusion: No significant association between the common genetic variants of SP-A and SP-D and SIDS is disclosed by the present study. However, low SP-A protein expression may possibly be determined by the 6A2/1A0 SP-A haplotype, this should be subject for further investigation. [source]

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma

A novel genetic variant of BMP2K contributes to high myopia

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2009
Hsin-Ping Liu
Abstract Loss of eye growth regulation may cause myopia, because modulation of optic globe size is essential for the generation of normal optic power. Evidence has implied variations of BMP2 gene expression mediate ocular development and retinal tissue remodeling. Given BMP2 as a potential regulator involved in myopia development, we investigate whether gene BMP2-inducible kinase (BMP2K, BIKe), whose expression is up-regulated during BMP2-induced osteoblast differentiation, contributes to susceptibility of high myopia. Participants grouped into high myopia had a spherical equivalent greater than ,6.00 D, compared with a control group of spherical equivalent less than ,0.5 D. Genotyping of polymorphisms 1379 G/A (rs2288255) and 3171 C/G (rs12507099), corresponding with 405 Gly/Ser and 1002 Thr/Ser variation in the BMP2K gene were determined by PCR-restriction fragment length polymorphism and associative study performed by comparing high myopic subjects and healthy controls. The frequency of A allele in the BMP2K gene 1379 G/A polymorphism showed a significant difference between cases and controls (P<0.001, OR=2.99, 95% CI=1.62,5.54) and subjects with either AA or AG genotype show higher risk than GG genotype (P<0.001, OR=3.07, 95% CI=1.59,5.92), while 3171 C/G polymorphism was not significant from this survey. These data suggest that BMP2K gene 1379 G/A variant is strongly correlated with high myopia and may contribute to a genetic risk factor for high degrees of myopic pathogenesis. J. Clin. Lab. Anal. 23:362,367, 2009. © 2009 Wiley-Liss, Inc. [source]

Association of RANTES promoter polymorphism with juvenile rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 4 2009
Tsung-Chieh Yao
Objective We recently reported that RANTES was a key molecule in the pathogenesis of juvenile rheumatoid arthritis (JRA) in a longitudinal cohort. This study was undertaken to investigate genetic associations between the RANTES ,28 C/G and ,403 G/A polymorphisms and JRA in a well-documented cohort of patients who were followed up prospectively. Methods Patients with JRA (n = 107) and healthy children (n = 139) were genotyped through use of a polymerase chain reaction,based assay. Association of the RANTES promoter polymorphisms with results of laboratory tests, clinical variables, outcome after clinical remission, and response to intraarticular triamcinolone injection was evaluated in patients who were followed up for >1 year. Results JRA patients had a significantly higher frequency of the RANTES ,28 G/G genotype, as compared with ethnically matched healthy controls. The RANTES ,28 C/G polymorphism was associated with the duration of clinical remission, with patients carrying the RANTES ,28G allele experiencing only 49% of the duration of remission experienced by patients who were RANTES ,28 C/C homozygous. The RANTES ,28 C/G polymorphism was associated with the duration of clinical response to intraarticular triamcinolone injection, with patients carrying the RANTES ,28G allele showing shorter duration of clinical response. No significant association between the RANTES ,403 G/A polymorphism and JRA was found in this Chinese population. Conclusion Our findings indicate that the RANTES ,28 C/G polymorphism represents a genetic risk factor for JRA. It is noteworthy that this RANTES promoter polymorphism was also associated with an early relapse of disease after clinical remission and a shorter duration of clinical response to intraarticular administration of corticosteroids. [source]

Chemokine RANTES Promoter Polymorphisms in Allergic Rhinitis,

THE LARYNGOSCOPE, Issue 4 2004
Jeong Joong Kim PhD
Abstract Objectives/Hypothesis RANTES is one of the most widely studied of the chemokines linked to allergic diseases. Two polymorphisms of the RANTES promoter region (,403 G/A and ,28 C/G) have been found. The authors investigated whether these RANTES promoter polymorphisms were associated with allergic rhinitis. Study Design Case-control study. Methods Blood samples for genetic analysis were obtained from 151 individuals with allergic rhinitis and from 278 healthy individuals without atopic disease. Polymerase chain reaction,based assays for detection of the ,403 G/A and ,28 C/G polymorphisms of the RANTES gene were used for genotyping. Results The frequencies of both the RANTES ,403A and ,28G alleles were significantly higher in patients with allergic rhinitis than in control subjects (P < .05 for both). Conclusion The study results indicated that the ,403 and ,28 alleles in the RANTES promoter region belong to the predictor gene set for allergic rhinitis and could be used in genomic analysis. [source]

Genetic polymorphisms in glutathione S-transferases T1, M1 and P1 and susceptibility to reflux esophagitis

DISEASES OF THE ESOPHAGUS, Issue 6 2006
B. Liu
SUMMARY., Recent studies indicate that the prevalence of reflux esophagitis (RE) in China is increasing. RE is one of the most common esophageal complications associated with gastroesophageal reflux disease (GERD) and RE-Barrett's esophagus-esophageal adenocarcinoma (EAC) sequence has been considered as an histogenesis model for EAC in Western countries. RE is only present in a subset of patients with GERD, suggesting an altered susceptibility to RE may exist in these GERD individuals. However, the genetic changes related with high susceptibility to RE is largely unknown. The polymorphisms in glutathione S-transferases (GSTs) T1, M1 and P1 have been reported with high susceptibity to esophageal cancer in Chinese people. The present case-control study was thus undertaken to characterize the genetic polymorphisms of GSTs and their correlation with susceptibility to RE. One hundred and nine patients with RE, 97 patients with nonerosive reflux disease (NERD) and 97 normal controls were recruited in this study. All the subjects were from Beijing, China, and received endoscopic examination and questionnaires for RE. Genomic DNA was extracted from the lymphocytes of peripheral blood for each subject. Genotypes of the GSTM1 and GSTT1 genes were analyzed by a multiplex PCR method. A,G polymorphism of codon 104 of the GSTP1 gene was detected using PCR-based restriction fragment length polymorphisms (RFLP). The variant GSTP1 genotypes (*A/*B,*B/*B) was found with a high frequency in the case with RE (40%), and followed by NERD (25%) and normal control (22%). The differences were statistically significant (P < 0.05). The risk for RE increased 2.42-fold [odds ratio (OR); 95% confidence interval (95% CI), 2.42 (1.22,4.80)] in the subjects with variant GSTP1 genotype. The subjects with positive variant GSTP1 genotypes and negative H. pylori infection showed increasing tendency for risk of RE [OR (95% CI), 2.67 (1.06,6.70)]. However, the subjects with GSTT1 and GSTM1 polymorphisms did not show any correlation with high risk for RE or NERD. No significant interactions were identified between the variant GSTs and cigarette smoking, or alcohol drinking and subtype of RE. The present result suggests that GSTP1 genetic polymorphism may be one of the high susceptibility factors involved in the mechanisms of RE. H. pylori infection may play a protective role against RE. [source]

Association between mitochondrial DNA 10398A>G polymorphism and the volume of amygdala

GENES, BRAIN AND BEHAVIOR, Issue 6 2008
H. Yamasue
Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders. [source]

Susceptibility to refractory ulcerative colitis is associated with polymorphism in the hMLH1 mismatch repair gene

INFLAMMATORY BOWEL DISEASES, Issue 6 2004
Siro Bagnoli MD
Abstract The hMLH1 gene lies in the linkage susceptibility region to inflammatory bowel disease (IBD) on 3p21. A single nucleotide polymorphism, 655A>G, in exon 8 of the gene causes an I219V change in the MLH1 protein. To test whether hMLH1 may confer susceptibility to ulcerative colitis (UC), we investigated an association between the 655A>G polymorphism and the disease. DNA-based technologies were used to analyze the 655A>G polymorphism in 201 UC patients and 126 healthy ethnically matched controls. The comparison of the allelic frequencies of the 655A>G polymorphism in UC patients and healthy controls did not show significant differences. However, genotype frequencies at the hMLH1 655 position were found to be significantly different when patients with and without refractory UC were compared. This was mainly attributable to a higher level of homozygosity for the G allele in refractory UC patients. Almost 5 times as many (4.9 times) refractory UC patients carried the GG genotype compared with nonrefractory patients (P < 0.0001). The present study provides evidence that the hMLH1 gene is involved in genetic susceptibility to refractory UC. If confirmed by other studies, the GG genotype at position 655 of the hMLH1 gene may represent a useful predictive factor for the clinical management of UC patients. [source]

Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2008
Fabio Farinati
Abstract Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori -induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1 -Cys326. The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C,G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C,G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C,G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status. © 2008 Wiley-Liss, Inc. [source]

Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2007
Fang Fang Zhang
Abstract Genetic variations increasing blood levels of acetaldehyde, the first metabolite of alcohol, refrain their carriers from drinking alcohol but may also put them at increased risk of cancer because of the mutagenic and carcinogenic effect of acetaldehyde. In a population-based study of 305 cases and 428 controls in Warsaw, Poland, we evaluated the effect of polymorphisms in alcohol metabolizing genes, including ADH1B (Ex9+5C>T, Ex3+23A>G, Ex3+58A>T and Ex9+77A>G), ADH1C (Ex8-56A>G and Ex6-14G>A) and ALDH2 (Ex1+82A>G), on levels of alcohol drinking and susceptibility of stomach cancer. We found that among control subjects frequency of alcohol drinking varied by alcohol metabolizing genotype. In particular, the weekly consumption of individuals carrying the AA, GA and GG genotypes of ALDH2 Ex1+82A >G polymorphism were 3.75, 2.26 and 1.53 drinks, respectively (p= 0.04). However, none of the assessed polymorphisms in these 3 genes had a measurable effect on stomach cancer risk. When stratified by ALDH2 Ex1+82A>G polymorphism, alcohol-related increases in stomach cancer risk were restricted to individuals with the AG/GG genotypes, with a more than 2-fold risk among daily drinkers (OR = 2.63, 95% CI = 1.00,6.88) and 3-fold risk (OR = 3.66, 95% CI = 1.19,11.24) among those with 40 or more drink-years. In summary, our results suggested that the ALDH2 Ex1+82 G allele may be functionally deficient in eliminating acetaldehyde and discourage alcohol drinking. Furthermore, heavy drinkers of alcohol who were genetically prone to accumulate acetaldehyde may face an increased risk of stomach cancer. © 2007 Wiley-Liss, Inc. [source]

Variation in the matrix metalloproteinase-3, -7, -12 and -13 genes is associated with functional status in rheumatoid arthritis

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2007
S. Ye
As matrix metalloproteinases (MMPs) play an important role in rheumatoid arthritis, we investigated whether variation in MMP genes was associated with functional disability in rheumatoid arthritis patients. A cohort of patients with seropositive rheumatoid arthritis were recruited and genotyped for the MMP1-1607 1G > 2G, MMP3-1612 5A > 6A, MMP7-153C > T, MMP7-181G > A, MMP12-82A > G and MMP13-77A > G polymorphisms. Genotypes were then analysed in relation to functional disability assessed by Steinbrocker index and Health Assessment Questionnaire (HAQ) score. We detected an association between the MMP13-77 A > G polymorphism and Steinbrocker index, with patients of the A/A genotype having higher score than patients of the A/G or G/G genotype (P = 0.005), and the association remained significant after adjusting for age, sex, erythrocyte sedimentation rate, presence of erosive disease, Ritchie score, prednisolone therapy and years of diagnosis (P = 0.003). We also observed a relationship of Steinbrocker index with the MMP3-1612 5A > 6A, MMP7-181 A > G and MMP12-82A > G polymorphisms (P = 0.082, P = 0.037 and P = 0.045). No association was detected between the MMP1-1607 1G > 2G and MMP7-153C > T polymorphisms and either Steinbrocker index or HAQ score. These results suggest that MMP3, MMP7, MMP12 and MMP13 genotypes may play a role in determining functional status of rheumatoid arthritis. [source]

OATP1B1 388A>G polymorphism and pharmacokinetics of pitavastatin in Chinese healthy volunteers

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2010
J. Wen PhD
Summary Purpose:, To investigate the contribution of the most frequent single nucleotide polymorphism (SNPs) of the organic anion transporting polypeptide 1B1 (OATP1B1) 388A>G to the pharmacokinetics of pitavastatin in Chinese healthy volunteers. Methods:, Eighteen healthy volunteers participated in this study. Group 1 consisted of nine subjects who were of 388AA wild-type OATP1B1 genotype. Group 2 consisted of seven subjects with the 388GA genotype and two 388GG homozygotes. Two milligram of pitavastatin was administered orally to the volunteers. The plasma concentration of pitavastatin was measured for up to 48 h by liquid chromatography,mass spectrometry (LC,MS). Results:, The pharmacokinetic parameters of pitavastatin were significantly different between the two genotyped groups. The concentration (Cmax) value was higher in the 388GA + 388GG group than that in the 388AA group (39·22 ± 8·45 vs. 22·90 ± 4·03 ng/mL, P = 0·006). The area under the curve to the last measurable concentration (AUC0,48) and area under the curve extrapolated to infinity (AUC0,,) of pitavastatin were lower in the 388AA group than in the 388GA + 388GG group (100·42 ± 21·19 vs. 182·19 ± 86·46 ng h/mL, P = 0·024; 108·12 ± 24·94 vs. 199·64 ± 98·70ng h/mL, P = 0·026) respectively. The oral clearance (Cl/F) was lower in the 388GA + 388GG group than that in the 388AA group (12·46 ± 4·79 vs. 19·21 ± 3·74/h, P = 0·012). The elimination of half-life (t1/2) and peak concentration times (Tmax) values showed no difference between these groups. Conclusions:, The OATP 388A>G polymorphism causes significant alterations in the pharmacokinetics of pitavastatin in healthy Chinese volunteers and this may well be clinically significant. [source]

Interleukin-27 polymorphisms are associated with inflammatory bowel diseases in a Korean population

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2009
Chun-Shi Li
Abstract Background and Aims:, The cytokine interleukin (IL)-27 is composed of two subunits, Epstein,Barr virus-induced gene 3 (EBI3) and p28, and IL-27 is a novel IL-12 family member that mediates between the innate and adaptive immune systems. We previously identified four polymorphisms in the human IL-27 gene and we suggested that the polymorphism of IL-27 is associated with the susceptibility to asthma. IL-27 transcripts are significantly elevated in active Crohn's disease (CD) but not in ulcerative colitis (UC). To determine whether these IL-27 single nucleotide polymorphisms are associated with the susceptibility to inflammatory bowel disease (IBD), the genotype and allelic frequencies of the IL-27 polymorphisms were analyzed between the IBD patients and the healthy controls. Methods:, Genotype analysis of the IL-27 gene was performed by the single-base extension (SBE) method. The haplotype frequencies of IL-27 for multiple loci were estimated using the expectation maximization (EM) algorithm. Results:, The genotype frequencies of the g.-964A > G polymorphism in the IBD patients were significantly different from those of the healthy control group (P = 0.001). In both the UC and CD patients, the genotype frequencies of the g.-964A > G polymorphism were also significantly different from the frequencies of the healthy control group (P = 0.009). The frequencies of the AGT and GGT haplotypes were significantly different between the healthy control group and the IBD patient group (P = 0.00004 and 0.021, respectively). Conclusion:, Our results suggest that the g.-964A > G polymorphism of the IL-27 gene located on the IBD1 locus might be associated with the susceptibility to IBD. [source]

The ,670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C

JOURNAL OF VIRAL HEPATITIS, Issue 6 2005
J. Aguilar-Reina
Summary., Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C virus (HCV) infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas. Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, ,1377G > A and ,670A > G. We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C. A cohort of 197 patients with chronic hepatitis C and 100 controls were analysed for both polymorphisms by Fluorescence Resonance Energy Transfer using specific probes and the LightcyclerTM system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system. We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection. However, we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the ,670A > G variant among those patients with higher Knodell's scores (P = 0.049) and necroinflammatory activity (P = 0.036). The ,670A allele was associated with higher levels of periportal necrosis (P = 0.012). In conclusion, our findings suggest an association between the ,670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C. [source]

The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs

ANIMAL GENETICS, Issue 1 2009
L. Fontanesi
Summary In humans, common variants in the fat mass and obesity associated (FTO) gene are associated with body mass index and obesity. Here we sequenced exon 4, parts of introns 3 and 4 and two portions of the 3,-untranslated region of the porcine FTO gene in a panel of nine pigs of different breeds and identified three SNPs. Allele frequencies of the g.276T>G (AM931150) mutation were studied in seven pig breeds. This mutation was used to linkage-map FTO to SSC6. Association analyses between the g.276T>G polymorphism and several traits [pH of semimembranosus muscle and estimated breeding values (EBV) for average daily gain, back fat thickness, lean cuts, ham weight and feed:gain ratio] were carried out in 257 sib-tested Italian Large White pigs. Only feed:gain ratio showed P < 0.05. A selective genotyping approach was applied, analysing two extreme and divergent groups of Italian Large White pigs selected on the basis of back fat thickness EBV (50 with most positive and 50 with most negative values). Fisher's exact test (two-tailed) was not significant when comparing the allele frequencies of these two groups. The same approach was used in the Italian Duroc breed for which two extreme and divergent groups of animals were selected according to visible intermuscular fat EBV. Differences of allele frequencies between these two groups were highly significant (P < 0.00001, P < 0.001 and P < 0.0001, considering all animals or only two- or three-generation unrelated animals respectively), indicating association between the analysed FTO marker and intermuscular fat deposition. [source]

The cholecystokinin type A receptor g.179A>G polymorphism affects feeding rate

ANIMAL GENETICS, Issue 2 2008
R. D. Houston
Summary A polymorphism within the 5, untranslated region of the cholecystokinin type A receptor (CCKAR) gene has been shown to affect feed intake and growth in commercial pig lines. To further investigate the phenotype of animals carrying alternative alleles at this polymorphism, we genotyped animals from a distinct segregating commercial line and an experimental cross F2 population, both with electronically recorded feeding pattern data. The data indicate that the daily feed intake increasing effect of the DQ496228:g.179G allele is mediated through a faster rate of feed intake, without evidence for an effect on other feeding behaviour traits. [source]

Association of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in Koreans

ANNALS OF HUMAN GENETICS, Issue 1 2009
H.-J. Lee
Summary Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 , 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population. [source]

The FAS ,670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes

ARTHRITIS & RHEUMATISM, Issue 12 2009
J. Broen
Objective To investigate the possible role of the FAS ,670A>G functional polymorphism in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. Methods A total of 2,900 SSc patients and 3,186 healthy controls were included in this study. We analyzed the genotype and allele frequencies of the FAS ,670A>G polymorphism in 9 distinct ethnic cohorts, including 6 cohorts of European ancestry (a Spanish cohort of 228 SSc patients and 265 controls, a Dutch cohort of 203 SSc patients and 277 controls, a German cohort of 313 SSc patients and 247 controls, an Italian cohort of 323 SSc cases and 89 controls, a British cohort of 269 SSc patients, and a Swedish cohort of 182 patients) and 3 distinct ethnic cohorts from the US (a cohort of 1,047 white patients and 692 controls, a cohort of 159 Hispanic patients and 137 controls, and a cohort of 176 black SSc patients and 194 controls). Genotyping was performed using a TaqMan 5, allelic discrimination assay. Results In the British, Italian, and American white cohorts we observed an association of the FAS ,670G allele with limited cutaneous SSc (lcSSc) (odds ratios [ORs] 1.25, 1.43, and 1.18, respectively). A meta-analysis comprising all 9 cohorts revealed an association of both the FAS ,670G allele (OR 1.10) and the FAS ,670GG genotype (OR 1.13) with the lcSSc phenotype. In a meta-analysis including only white subjects, both the FAS ,670G allele and the FAS ,670GG genotype remained associated with lcSSc (allele OR 1.12; genotype OR 1.16). In addition, a recessive model of the ,670GG genotype exhibited a strong association with SSc, lcSSc, and anticentromere antibody,positive lcSSc (OR 1.23, OR 1.33, and OR 1.45, respectively). Conclusion Our data show that the FAS ,670A>G polymorphism plays a role in lcSSc susceptibility. A similar trend has been observed in other autoimmune diseases. [source]

Fluctuation in self-perceived stress and increased risk of flare in patients with lupus nephritis carrying the serotonin receptor 1A ,1019 G allele

ARTHRITIS & RHEUMATISM, Issue 10 2006
Daniel J. Birmingham
Objective Stress is believed to be a risk factor for systemic lupus erythematosus (SLE) flare. Two serotonin-related gene polymorphisms, the serotonin receptor 1A (5-HT1A) polymorphism at ,1019C>G and the serotonin transporter LS polymorphism, have been reported to affect stress-related behaviors. The purpose of this study was to assess the relationship between self-perceived stress (SPS), variability in SPS, and the 2 serotonin-related gene polymorphisms as risk factors for SLE flare. Methods Seventy-seven SLE patients (50 with lupus nephritis) were evaluated every 2 months (mean ± SD total followup 18.5 ± 8.5 months), and patients recorded their daily SPS levels (0,10 scale). Values for mean SPS and coefficient of variation (CV) for SPS were calculated from the 60-day block of daily measurements between study visits. Serotonin-related gene polymorphism genotypes were determined by polymerase chain reaction,based methods. Results Of the 77 patients, 53 experienced 80 flares of SLE (32 renal flares) based on prespecified criteria. Multivariate analysis revealed that whereas neither the serotonin-related gene polymorphisms nor the mean SPS was predictive of an SLE flare, an increased CV for SPS was predictive (P = 0.0031). Interaction between the CV for SPS and the 5-HT1A ,1019C>G polymorphism was also found to be a predictor of SLE flare (P = 0.0039). Subset analysis revealed that only in lupus nephritis patients were increasing CVs for SPS (P = 0.0002) and the interaction between CVs for SPS and 5-HT1A (P < 0.0001) predictive of a flare. Odds ratio curves demonstrated that the predictive effect of increasing CVs for SPS required the presence of the 5-HT1A ,1019 G allele, but appeared to be independent of the G allele number. Conclusion Fluctuation in the level of SPS is a risk factor for the onset of flare in SLE patients with major renal manifestations when it occurs on the background of a stress-related susceptibility gene (the 5-HT1A ,1019 G allele). [source]

Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: The Self Defense Forces Health Study

CANCER SCIENCE, Issue 3 2008
Naoyuki Ueda
Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX-2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX-2 polymorphisms (,1195G>A, ,765G>C and 8160A>G) to colorectal adenomas in a case,control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non-significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of ,1195G>A polymorphism and for the GC versus GG genotype of ,765G>C polymorphism. None had the ,765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either ,1195G>A or ,765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of ,1195G, ,765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99,1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04,2.38). Another haplotype of ,1195A, ,765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06,0.88). These findings add to evidence for the role of COX-2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes. (Cancer Sci 2008; 99: 576,581) [source]

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma

Variation in the matrix metalloproteinase-3, -7, -12 and -13 genes is associated with functional status in rheumatoid arthritis

Lack of association between NPHS2 gene polymorphisms and sporadic IgA nephropathy

NEPHROLOGY, Issue 4 2007
JIANHUA MAO
SUMMARY: Aim: IgA nephropathy (IgAN) is the most common primary form of glomerulonephritis worldwide. In the present study, the genetic structure of the NPHS2 gene was studied to verify if podocin plays a role in the pathogenesis of IgAN. Methods: Clinical characteristics and DNA samples were collected from 26 Chinese children with sporadic IgAN. A direct sequencing was performed after polymerase chain reaction amplification to all the eight exons of the NPHS2 gene. Results: Three synonymous variants as known polymorphisms (954T,C homozygous, 1038A,G heterozygous and homozygous) were found in 3, 4 and 1 patients, respectively. There was no significant difference in the genotypic and allelic frequencies of 954T > C and 1038A > G polymorphisms between the patients and normal controls. Conclusion: No significant difference in the genotypic and allelic frequencies of the identified 954T > C and 1038A > G polymorphisms between the patients and normal controls was found. [source]

Polymorphisms in ERCC2, MSH2, and OGG1 DNA repair genes and gallbladder cancer risk in a population of Northern India

CANCER, Issue 13 2010
Kshitij Srivastava MSc
Abstract BACKGROUND: Genetic variants of DNA repair enzymes may lead to genetic instability and contribute to gallbladder (GB) carcinogenesis. METHODS: A case-control study (230 GB carcinogenesis patients and 230 controls) was undertaken to evaluate whether genetic variations in 3 DNA repair genes ERCC2 (Asp312Asn [rs1799793] and Lys751Gln [rs13181]), MSH2 (,118T>C [rs2303425] and IVS1 + 9G>C [rs2303426]), and OGG1 (Ser326Cys [rs1052133] and 748-15C>G [rs2072668]) are associated with GB carcinogenesis risk in a North Indian population. RESULTS: The authors found that the ERCC2 Asp312Asn AA, MSH2 IVS1 + 9G>C CC, OGG1 Ser326Cys GG and CG + GG, and OGG1 748-15C>G GG and CG + GG genotypes were significantly associated with an increased risk of GB carcinogenesis (odds ratio [OR], 2.1, 1.8, 2.5, 1.8, 2.0, and 1.6, respectively). In contrast, ERCC2 Lys751Gln, and MSH2 ,118T>C markers showed no significant associations with GB carcinogenesis risk, although because of the small sample size their effects cannot be ruled out. Female GB carcinogenesis patients with the OGG1 748-15C>G GG, OGG1 Ser326Cys GG, and ERCC2 Asp312Asn genotypes had a greater risk for developing the disease (OR, 3.6, 7.7, and 2.7, respectively). There was a significant interaction between MSH2 IVS1 + 9G>C and OGG1 748-15C>G polymorphisms (P = .001). Furthermore, individuals with >6 variant alleles of the studied polymorphisms were at 4-fold increased risk for developing GB carcinogenesis. Classification and Regression Tree analysis revealed potential higher-order gene-gene interactions and categorized a few higher-risk subgroups for GB carcinogenesis. CONCLUSIONS: These results suggest that genetic variants in the DNA repair pathways may be involved in GB carcinogenesis etiology. Cancer 2010. © 2010 American Cancer Society. [source]

Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancer

CANCER, Issue 4 2008
Ji-Youn Han MD
Abstract BACKGROUND. The purpose of the study was to investigate whether polymorphisms of p53 codon 72 (Arg72Pro) and MDM2 SNP309 (309T>G) affect p53 expression and the clinical outcome of patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. A total of 148 NSCLC patients, previously enrolled in 2 different prospective clinical trials, were genotyped for the p53 Arg72Pro and MDM2 309T>G polymorphisms. Immunohistochemical staining of p53 protein was performed on 61 tumor samples. Genotypes were correlated with p53 expression, clinicopathologic factors, tumor response, and survival. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables. RESULTS. The distribution of sex, age, performance status, stage, tumor histology, and smoking habit was not significantly different among polymorphism variants. However, a significant association was observed between p53 Arg72Pro polymorphism and primary resistance to chemotherapy. Patients with the Pro/Pro variant were more likely to be resistant to first-line chemotherapy, especially the irinotecan plus cisplatin regimen, than those with Arg/Arg or Arg/Pro variants (60% vs 27%, P = .014). In multivariate analysis, the Pro/Pro genotype was strongly predictive for shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, P = .01). The p53 overexpression was associated with MDM2 SNP309. The TT genotype showed more p53 overexpression than TG or GG genotypes (P = .036). In multivariate analysis, the MDM2 TT genotype was independently predictive for longer survival (HR = 1.742, P = .032). CONCLUSIONS. The p53 72Pro/Pro variant was predictive for primary resistance to chemotherapy and shorter progression-free survival. The MDM2 SNP309 was associated with less p53 overexpression and prognostic for worse survival. Genotyping these polymorphisms may be useful for predicting the clinical outcome of advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. [source]

Cloninger's temperament dimensions and epidermal growth factor A61G polymorphism in Finnish adults

GENES, BRAIN AND BEHAVIOR, Issue 1 2006
L. Keltikangas-Järvinen
This study examines a link between human temperament and epidermal growth factor (EGF). There is evidence that dopaminergic neurotransmission in the central nervous system has a role in temperament, especially in novelty seeking. Functional polymorphism in EGF gene has an impact on EGF production, and EGF, in turn, appears to affect the development of midbrain dopaminergic neurons. Epidermal growth factor gene A61G polymorphisms were studied in a randomly selected sample of 292 Finnish adults. Their temperaments were assessed twice (with a 4-year test,retest interval) with Cloninger's Temperament and Character Inventory consisting of four dimensions, i.e. novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P). The findings on men showed a significant association between a presence of the G/G polymorphism and scoring in the highest tertile on NS in both test and retest. The same was true with men who scored high on RD, especially on sensitivity, in both tests. Among women, G/G polymorphism was associated with a stable high level of P. Importantly, temperament dimensions, as assessed with one test only, did not provide replicable associations with EGF polymorphism across the two measurements. Our results demonstrate the importance of reliable phenotype assessment and lend support to the hypothesis that dopaminergic activity is one factor underlying stable temperament. [source]