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Insertion/deletion Polymorphism (deletion + polymorphism)
Selected AbstractsRole of angiotensin-converting enzyme gene polymorphisms in children with sepsis and septic shockPEDIATRICS INTERNATIONAL, Issue 4 2008Ozgur Cogulu Abstract Background: Sepsis is characterized by a systemic inflammatory response. Its development and outcome are associated with host defense, pathogenicity of the microorganism and genetic polymorphisms. Genetic polymorphisms of the immune system genes have been shown to have a close relationship with the clinical outcomes of sepsis. Angiotensin-converting enzyme (ACE) plays a major role in the host defense against invading pathogens. It is therefore likely that polymorphisms in the ACE gene may have an important effect on determining the development and the outcome of sepsis. Methods: Ninety-eight children diagnosed as having sepsis and 287 healthy children were included in the study. Insertion/deletion polymorphisms were analyzed using reverse-hybridization assay. Results: The carriers of I allele (D/I genotype and I/I genotype) were found to have an increased risk of developing sepsis compared to the controls. Conclusion: DD genotype may play a positive role against the development of sepsis in healthy children. [source] Assessing interethnic admixture using an X-linked insertion-deletion multiplexAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2009Elzemar Martins Ribeiro-Rodrigues In this study, a PCR multiplex was optimized, allowing the simultaneous analysis of 13 X-chromosome Insertion/deletion polymorphisms (INDELs). Genetic variation observed in Africans, Europeans, and Native Americans reveals high inter-population variability. The estimated proportions of X-chromosomes in an admixed population from the Brazilian Amazon region show a predominant Amerindian contribution (,41%), followed by European (,32%) and African (,27%) contributions. The proportion of Amerindian contribution based on X-linked data is similar to the expected value based on mtDNA and Y-chromosome information. The accuracy for assessing interethnic admixture, and the high differentiation between African, European, and Native American populations, demonstrates the suitability of this INDEL set to measure ancestry proportions in three-hybrid populations, as it is the case of Latin American populations. Am. J. Hum. Biol. 2009. © 2009 Wiley-Liss, Inc. [source] Effects of structural variations of APOBEC3A and APOBEC3B genes in chronic hepatitis B virus infectionHEPATOLOGY RESEARCH, Issue 12 2009Hiromi Abe Aim:, Human APOBEC3 deaminases induce G to A hypermutation in nascent DNA strand of hepatitis B virus (HBV) genomes and seem to operate as part of the innate antiviral immune system. We analyzed the importance of APOBEC3A (A3A) and APOBEC3B (A3B) proteins, which are potent inhibitors of adeno-associated-virus and long terminal repeat (LTR)-retrotransposons, in chronic HBV infection. Methods:, We focused on the common deletion polymorphism that spans from the 3, part of A3A gene to the 3, portion of A3B gene. An association study was carried out in 724 HBV carriers and 469 healthy control subjects. We also analyzed hypermutated genomes detected in deletion and insertion (non-deletion) homozygous patients to determine the effect of APOBEC3 gene deletion. Further, we performed functional analysis of A3A gene by transient transfection experiments. Results:, The association study showed no significant association between deletion polymorphism and chronic HBV carrier state. Context analysis also showed a negligible effect for the deletion. Rather, mild liver fibrosis was associated with APOBEC gene deletion homozygosity, suggesting that A3B deletion is not responsible for chronic HBV infection. Functional analysis of A3A showed that overexpression of A3A induced hypermutation in HBV genome, although the levels of hypermutants were less than those introduced by A3G. However, overexpression of A3A did not decrease replicative intermediates of HBV. Conclusion:, These results suggest that A3A and A3B play little role in HBV elimination through anti-viral defense mechanisms. The significance of hypermutation induced by A3A should be investigated further. [source] Parallel effects of genetic variation in ACE activity in baboons and humansAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2007Jenny Tung Abstract Like humans, savannah baboons (Papio sp.) show heritable interindividual variation in complex physiological phenotypes. One prominent example of such variation involves production of the homeostatic regulator protein angiotensin converting enzyme (ACE), which shows heritable variation in both baboons and humans. In humans, this phenotypic variation is associated with an Alu insertion,deletion polymorphism in the ACE gene, which explains approximately half of the variation in serum ACE activity. We identified a similar Alu insertion,deletion polymorphism in the baboon ACE homologue and measured its frequency in a wild population and a captive population of baboons. We also analyzed the contribution of ACE genotype at this indel to variation in serum ACE activity in the captive population. When conditioned on weight, a known factor affecting ACE activity in humans, age and ACE genotype both accounted for variance in ACE activity; in particular, we identified a significant nonadditive interaction between age and genotype. A model incorporating this interaction effect explained 21.6% of the variation in residual serum ACE activity. Individuals homozygous for the deletion mutation exhibited significantly higher levels of ACE activity than insertion,deletion heterozygotes at younger ages (10,14 years), but showed a trend towards lower levels of ACE activity compared with heterozygotes at older ages (,15 years). These results demonstrate an interesting parallel between the genetic architecture underlying ACE variation in humans and baboons, suggesting that further attention should be paid in humans to the relationship between ACE genetic variation and aging. Am J Phys Anthropol, 2007. © 2007 Wiley-Liss, Inc. [source] Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patientsDIABETIC MEDICINE, Issue 8 2003S. Hadjadj Abstract Aims Family-based studies suggest a genetic basis for nephropathy in Type 2 diabetes. The angiotensin-I-converting enzyme (ACE) gene is a candidate gene for Type 1 diabetes nephropathy. We assessed the association between high urinary albumin concentration and ACE insertion/deletion (I/D) polymorphism, in French Type 2 diabetes patients. Methods We studied 3139 micro/macroalbuminuric French patients recruited in the DIABHYCAR Study, an ACE inhibition trial in Type 2 diabetes patients with renal and cardiovascular outcomes. The main inclusion criteria were age , 50 years, urinary albumin concentration , 20 mg/l assessed centrally during two consecutive screening visits, and plasma creatinine concentration , 150 µmol/l. These patients were compared with 605 normoalbuminuric (NA; urinary albumin concentration < 10 mg/l at first screening for the DIABHYCAR Study) French patients. ACE I/D genotype was determined by nested polymerase chain reaction. Results The ACE I/D polymorphism was in Hardy,Weinberg equilibrium. The distribution of genotypes did not differ significantly between micro/macroalbuminuric and NA patients: 552 and 115 II, 1468 and 282 ID, 1119 and 208 DD (P = 0.67). However, the ACE D allele was more frequent among normotensive micro/macroalbuminuric patients than among NA patients (P = 0.039). Conclusions The ACE I/D polymorphism was not associated with high urinary albumin concentration in French Type 2 diabetes patients. [source] No Influence of 5-HTTLPR Gene Polymorphism on Migraine Symptomatology, Comorbid Depression, and ChronificationHEADACHE, Issue 3 2010Thomas Wieser MD (Headache 2010;50:420-430) Background., The serotonergic system is thought to play an important role for mediating susceptibility to migraine and depression, which is frequently found comorbid in migraine. The functional polymorphism in the serotonin transporter gene linked polymorphic region (5-HTTLPR/SLC6A4) was previously associated with attack frequency and, thus, possibly with chronification. Objective., We hypothesized that patients with the "s" allele have higher attack frequency and, paralleling results in depression research, higher scores of depression. Methods., Genetic analysis of the SLC6A4 44 bp insertion/deletion polymorphism (5-HTTLPR) was performed in 293 patients with migraine with and without aura. Self-rating questionnaires were used for assessment of depression. Results., Multinomial logistic regression analysis found no evidence for association of the 5-HTTLPR polymorphism with either depression or migraine attack frequency. Conclusion., We were not able to demonstrate any influence of the serotonin transporter 5-HTTLPR polymorphism on migraine phenomenology (attack frequency or comorbid depression), thereby excluding this variant to be a common genetic denominator for chronic migraine and depression. [source] Polymorphisms in fatty acid-binding protein-3 (FABP3) , putative association with type 2 diabetes mellitus,,HUMAN MUTATION, Issue 2 2003Hyoung Doo Shin Abstract Fatty acid-binding proteins (FABPs) play key roles as transport vehicles of fatty compounds throughout the cytoplasm. Human FABP3, one of the FABPs, is present in a wide variety of tissues with highest concentration in cardiac and skeletal muscle. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced the full gene of FABP3, including the ,1,500bp promoter region. Fourteen polymorphisms were identified in FABP3: two ins/dels, two STRs, and ten SNPs (two in promoter, nine in intron, two in 3'UTR, and one in the 3' end). Among identified polymorphisms, five common sites including c.-530underscore;-532delCTC, c.-345T>C, c.348+429(CA)9-18, c.246+1806G>C, and c.634+483delT were genotyped in subjects with type 2 diabetes mellitus and normal control (n=669). By logistic and multiple regression analysis, one insertion/deletion polymorphism in the 3' end (c.634+483delT) of FABP3 appeared to be weakly associated with increased risk of type 2 diabetes (OR=1.78,1.94, P=0.03,0.04) and waist/hip ratio (WHR) (P=0.03). © 2003 Wiley-Liss, Inc. [source] Role of the NFKB1 ,94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genesINFLAMMATORY BOWEL DISEASES, Issue 7 2006Jürgen Glas MD Abstract Background: Recently, an association of the NFKB1 polymorphism ,94ins/delATTG with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion polymorphism is localized in the promoter region of the NFKB1 gene and appears to be functionally relevant. The aim of the present study was to confirm the association of the ,94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a population of German origin and to test for a potential association with Crohn's disease (CD). Furthermore, potential interactions of the ,94ins/delATTG polymorphism with the IKBL and the IL-1RN genes should be determined. Materials and Methods: The study population comprised 630 patients with CD, 365 patients with UC, and 974 healthy controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. For statistical evaluation, the chi-square test and the Fisher exact test were used. Results: No significant association of the W/D NFKB1 polymorphism with CD or UC was detected. In addition, no significant interactions between the ,94ins/delATTG NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes, respectively, were found in CD or UC. Also, no significant interactions of the NFKB1 polymorphism with mutations of the CARD15/NOD2 gene and with clinical phenotypes were detected in CD. Moreover, no associations of the NFKB1 polymorphism were found in UC depending on disease localization. Conclusions: The present study could not confirm the reported association of the ,94ins/delATTG NFKB1 polymorphism with UC and also found no evidence for a role of this polymorphism in CD. The results do not give evidence for a role of this NFKB1 polymorphism in the pathogenesis of UC and CD. [source] High levels of MMP-1 expression in the absence of the 2G single nucleotide polymorphism is mediated by p38 and ERK1/2 mitogen-activated protein kinases in VMM5 melanoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2002Ulrike Benbow Abstract Matrix metalloproteinase-1 (MMP-1) is one of only a few enzymes with the ability to degrade the stromal collagens (types I and III) at neutral pH, and high expression of MMP-1 has been associated with aggressive and invasive cancers. We recently reported a single nucleotide insertion/deletion polymorphism (SNP) in the collagenase-1 (MMP-1) promoter (Rutter et al. [1998] Can. Res. 58:5321,5325), where the insertion of an extra guanine (G) at ,1607 bp creates the sequence, 5,-GGAA-3 (2G allele), compared to the sequence 5,-GAA-3, (1G allele). The presence of 2G constitutes a binding site for the ETS family of transcription factors, and increases MMP-1 transcription in fibroblasts and A2058 melanoma cells cultured in vitro. In addition, the presence of the 2G allele has been linked to several aggressive malignancies as well as to enhanced expression of MMP-1. In this study, we describe a melanoma cell line, VMM5, that is 1G homozygous, but that is invasive and expresses high levels of MMP-1 constitutively. The high level of MMP-1 expression in VMM5 cells is due to the utilization of both the p38 and ERK1/2 transduction pathways. In contrast, in the A2058 cell line, which also expresses MMP-1 constitutively and which is 2G homozygous, only the ERK pathway is activated. Thus, our data suggest that in the absence of 2G allele and in the presence of the appropriate transcription factors, tumor cells may use alternative signal/transduction pathways and cis-acting sequences to achieve high levels of MMP-1 expression, which contribute to the ability of tumor cells to invade, regardless of their genotype. © 2002 Wiley-Liss, Inc. [source] Association of low density lipoprotein receptor related protein-associated protein (LRPAP1) gene insertion/deletion polymorphism with gallstone diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2006MANJUSHA DIXIT Abstract Background and Aim:, Gallstones are byproducts of cholesterol supersaturated bile. Various studies have indicated that there might be a genetic predisposition to the disease. Receptor-associated protein (RAP) is a molecular chaperone for low density lipoprotein receptor-related protein (LRP), which plays a key role in cholesterol metabolism. Intron 5 insertion/deletion polymorphism of RAP gene (LRPAP1) has been implicated in other diseases sharing etiology with gallstone disease (GSD). Methods:, To analyze the association of insertion/deletion polymorphism in GSD, 130 gallstone patients and 202 healthy subjects took part in the present study. For genotyping, polymerase chain reaction was followed by 2% agarose gel electrophoresis. Results:, The results showed that frequencies of D and I allele were 65.77% and 34.23% in patients, 76.24% and 23.76% in controls, respectively. Frequency of I allele was significantly higher in the patient group than in the control group (P = 0.003). Conclusion:, In the present study I (insertion) allele was found to be associated with GSD. [source] DHFR 19-bp insertion/deletion polymorphism and MTHFR C677T in adult acute lymphoblastic leukaemia: Is the risk reduction due to intracellular folate unbalancing?,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Donato Gemmati First page of article [source] Hypertension and ace gene insertion/deletion polymorphism in pediatric renal transplant patientsPEDIATRIC TRANSPLANTATION, Issue 5 2005Erkin Serdaroglu Abstract:, The objective of the present study was to define the risk factors for hypertension and to analyze the influence of insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) on hypertension in pediatric renal transplant recipients. Twenty-six pediatric renal transplant recipients with stable renal function and treated with the same immunosuppression protocol were included in the study. Their mean age was 12.5 ± 3.3 yr and mean time after transplantation was 38.5 ± 39.8 month. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed by SpaceLabs (90207) device. The I/D polymorphism of the ACE was determined by PCR and ACE serum level was analyzed by colorimetric method. Hypertension was present in 15 patients (57.7%) by causal blood pressure measurements and 19 patients (73.1%) by ABPM. Twenty-two patients (84.6%) were found to be non-dipper and eight of them had reverse dipping. Only time after transplantation (38 ± 31 vs. 79 ±49 month, p = 0.016) and cyclosporin A trough plasma levels (206 ±78 vs. 119 ± 83 ng/mL, p = 0.020) influenced the presence of hypertension by multiple logistic regression analysis. The distribution of genotypes were II = 2 (7.7%), ID = 8 (30.8%), DD = 16 (61.5%). There was no effect of ACE gene I/D polymorphism or serum ACE levels on hypertension prevalence and circadian variability of blood pressures. Hypertension was related to the time after transplantation and cyclosporin A levels. The ACE gene I/D polymorphism and serum ACE levels did not influence the blood pressure values or circadian variability of blood pressure among pediatric renal transplant patients. [source] Molecular genetics of bipolar disorder and depressionPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2007TADAFUMI KATO md Abstract, In this review, all papers relevant to the molecular genetics of bipolar disorder published from 2004 to the present (mid 2006) are reviewed, and major results on depression are summarized. Several candidate genes for schizophrenia may also be associated with bipolar disorder: G72, DISC1, NRG1, RGS4, NCAM1, DAO, GRM3, GRM4, GRIN2B, MLC1, SYNGR1, and SLC12A6. Of these, association with G72 may be most robust. However, G72 haplotypes and polymorphisms associated with bipolar disorder are not consistent with each other. The positional candidate approach showed an association between bipolar disorder and TRPM2 (21q22.3), GPR50 (Xq28), Citron (12q24), CHMP1.5 (18p11.2), GCHI (14q22-24), MLC1 (22q13), GABRA5 (15q11-q13), BCR (22q11), CUX2, FLJ32356 (12q23-q24), and NAPG (18p11). Studies that focused on mood disorder comorbid with somatic symptoms, suggested roles for the mitochondrial DNA (mtDNA) 3644 mutation and the POLG mutation. From gene expression analysis, PDLIM5, somatostatin, and the mtDNA 3243 mutation were found to be related to bipolar disorder. Whereas most previous positive findings were not supported by subsequent studies, DRD1 and IMPA2 have been implicated in follow-up studies. Several candidate genes in the circadian rhythm pathway, BmaL1, TIMELESS, and PERIOD3, are reported to be associated with bipolar disorder. Linkage studies show many new linkage loci. In depression, the previously reported positive finding of a gene,environmental interaction between HTTLPR (insertion/deletion polymorphism in the promoter of a serotonin transporter) and stress was not replicated. Although the role of the TPH2 mutation in depression had drawn attention previously, this has not been replicated either. Pharmacogenetic studies show a relationship between antidepressant response and HTR2A or FKBP5. New technologies for comprehensive genomic analysis have already been applied. HTTLPR and BDNF promoter polymorphisms are now found to be more complex than previously thought, and previous papers on these polymorphisms should be treated with caution. Finally, this report addresses some possible causes for the lack of replication in this field. [source] An insertion/deletion polymorphism in the fourth intron of POP5 is used for linkage mapping in sheepANIMAL GENETICS, Issue 3 2002C. Diez-Tascón No abstract is available for this article. [source] Linkage mapping of the ovine ANLN gene using an insertion/deletion polymorphismANIMAL GENETICS, Issue 3 2002C. Diez-Tascón No abstract is available for this article. [source] The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndromeARTHRITIS & RHEUMATISM, Issue 7 2009Corinne Miceli-Richard Objective Interferon regulatory factor 5 is a transcription factor involved in type I interferon (IFN) secretion. This study was undertaken to investigate whether a 5-bp (CGGGG insertion/deletion) promoter polymorphism is involved in genetic predisposition to primary Sjögren's syndrome (SS) and to assess the functional consequences of this polymorphism. Methods The exploratory cohort consisted of 185 patients with primary SS and 157 healthy controls, and the replication cohort consisted of 200 patients with primary SS and 282 healthy controls. Levels of IRF5 messenger RNA (mRNA) were assessed at baseline and after in vitro infection with reovirus in peripheral blood mononuclear cells (PBMCs) from 30 patients with primary SS and from salivary gland epithelial cells that had been cultured for 4 weeks from patients with primary SS or sicca symptoms. Results Carriage of the IRF5 4R CGGGG allele was associated with a greatly increased risk of primary SS in both cohorts (odds ratio 2.00 [95% confidence interval 1.5,2.7], P = 6.6 × 10,6). The CGGGG insertion/deletion polymorphism alone was sufficient to explain the association of primary SS with IRF5. The level of IRF5 mRNA in PBMCs depended significantly on genotype (P = 0.002) and was correlated with the levels of mRNA for the IFN-induced genes MX1 and IFITM1. Cultured salivary gland epithelial cells from patients carrying the 4R CGGGG IRF5 allele showed a high level of IRF5 mRNA (P = 0.04), which was amplified after reovirus infection (P = 0.026). Conclusion Our findings indicate an association of the CGGGG insertion/deletion polymorphism of the IRF5 promoter with primary SS. Patients carrying the 4R CGGGG IRF5 allele had a high level of mRNA for IRF5 in PBMCs and salivary gland epithelial cells, mainly after in vitro viral infection. Patients with high levels of mRNA for IRF5 also had high levels of mRNA for type I IFN,induced genes in PBMCs. [source] Real-time PCR quantification of haematopoietic chimerism after transplantation: a comparison between TaqMan and hybridization probes technologiesINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p1 2010J. MARTINEZ-LOPEZ Summary This study aimed to compare the sensitivity and accuracy of two methods of quantitative real-time polymerase chain reaction (qrt-PCR), in order to determine haematopoietic chimerism (CH): single nucleotide polymorphisms using TaqMan (TM) probes and insertion/deletion polymorphisms using Hybridization (Hyb) probes. A total of 106 samples from 20 patients who underwent allogenic stem cell transplantation (n = 14) or live-donor liver transplantation (n = 6) were studied. The mean level of chimerism was 8.37% for the TM method and 7.73% in the Hyb method, which was not significantly different (P = 0.69). The Pearson correlation coefficient between the two methods was r = 0.91 (P < 0.001). The estimation of the regression line, using the Passing and Balbock method was Intercept A ,0.0381 [95% confidence interval (CI) ,0.1265 to 0.0296) and Slope B: 1.04609(95% CI 0.9349,1.161). Bland,Altman data showed that the standard deviations, which differed between the two methods (%Hyb,%TM), were 0.98 and ,1.28. The accuracy and sensitivity of qrt-PCR chimerism is independent of the method used if the optimization is adequate and satisfies the criteria for adequate study. Real-time PCR, independent of the method adopted, is a very good tool for study levels of CH. [source] | |||||||||||||