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Polymerase Chain Reaction-restriction Fragment Length Polymorphism (polymerase + chain_reaction-restriction_fragment_length_polymorphism)
Terms modified by Polymerase Chain Reaction-restriction Fragment Length Polymorphism Selected AbstractsDetermination of ABCB1 polymorphisms and haplotypes frequencies in a French populationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007Elise Jeannesson Abstract The ATP-binding cassette (ABC) transporter ABCB1, or P-glycoprotein, is a transmembrane efflux pump well known for its implication in drug transport and chemoresistance. ABCB1 substrates include either drugs, such as antiretrovirals and immunomodulators, or physiological molecules like phospholipids. Pharmacogenetic analysis of ABCB1 polymorphisms, in addition to other xenobiotic metabolizing enzymes, might help to personalize and optimize drug therapy. Indeed, some polymorphisms of ABCB1 have been implicated in susceptibility to diseases, changes in drug pharmacokinetics, and in variation of the biological response to drug treatment. In addition, variant and haplotype distributions differ depending on ethnicity. Thus, some ethnies may be at higher risk for adverse events, inefficacy of treatment or prevalence of pathologies. This study aimed to determine frequencies of ABCB1 polymorphisms and haplotypes in a sample of French healthy individuals. DNA was isolated from blood-EDTA. Polymerase chain reaction-restriction fragment length polymorphism and TaqMan single nucleotide polymorphism genotyping assays were used to genotype 227 individuals for T-129C, G-1A, A61G, G1199A, C1236T, T-76A, G2677T/A and C3435T polymorphisms. The observed frequencies of the variant allele for these eight polymorphisms are 0.04, 0.08, 0.09, 0.06, 0.42, 0.46, 0.45 and 0.46 respectively. These polymorphisms are in linkage disequilibrium and haplotype frequencies were determined, the most frequent haplotype being the one with variants at position 1236, 2677 and 3435 and wild-type alleles at the other positions. Finally, the frequencies of these eight ABCB1 polymorphisms in our French individuals supposed to be healthy population are quite similar to those described in other Caucasian populations except for the C3435T polymorphism. [source] Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1, gene and the relationship to ,-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitusDIABETIC MEDICINE, Issue 12 2004J. Lauenborg Abstract Aims In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to ,-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1, (HNF-1,) gene has been associated with decreased serum insulin and C-peptide responses during an oral glucose tolerance test (OGTT) in glucose-tolerant subjects. The aims of the present study were to evaluate the influence of the polymorphism on the serum insulin and C-peptide responses to an OGTT in glucose-tolerant women with and without previous GDM and to investigate if this polymorphism is associated with GDM. Methods The Ala/Val98 polymorphism was measured in 376 women of Danish origin with previous GDM, and in 724 age-matched and 310 middle-aged glucose tolerant women using polymerase chain reaction-restriction fragment length polymorphism. Results The allelic frequency of the Ala/Val98 polymorphism was 0.043 [95% confidence interval (CI) 0.028, 0.057] in women with previous GDM vs. 0.037 (95% CI 0.028, 0.047) in age-matched and 0.039 (95% CI 0.024, 0.054) in middle-age women. Among 117 glucose-tolerant women with previous GDM, 10 carriers of the Ala/Val98 polymorphism had a non-significant 27% and 22% reduction in serum C-peptide and insulin levels, respectively, at 30 min during an OGTT. Seventy-eight control subjects carrying the Ala/Val98 polymorphism had a 10% (P = 0.001) and 16% (P = 0.004) reduction in serum C-peptide and insulin levels, respectively, compared with 956 Ala/Ala control subjects. Conclusions The Ala/Val polymorphism at codon98 of HNF-1, is not associated with GDM in Danish women. However, the codon 98 variant is associated with a significant impairment of serum insulin and C-peptide responses during an OGTT in glucose-tolerant women without previous GDM. [source] Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosisENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2009Shan Kang Abstract Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (,2578C/A, ,1154G/A, ,460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 174 adenomyosis patients and 199 frequency-matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the ,2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42,0.97]. For the ,1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33,0.80). However, the genotype distributions and allele frequencies of the ,460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF ,460/,1154/,2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41,1.00; OR = 0.44, 95% CI = 0.21,0.93, respectively). The study indicated that the ,2578A or ,1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development. Environ. Mol. Mutagen., 2009. © 2009 Wiley-Liss, Inc. [source] Molecular investigation on strain genetic relatedness and population structure of Beauveria bassianaENVIRONMENTAL MICROBIOLOGY, Issue 10 2003Chengshu Wang Summary Triplicate molecular methods, i.e. polymerase chain reaction-restriction fragment length polymorphism of the pr1 gene, microsatellite markers and 28S rDNA haplotyping by detecting the presence or absence of group I introns, were used for population study of the entomopathogenic fungus, Beauveria bassiana. The findings showed that the average genetic diversity index of geographical populations was significantly smaller than that of populations derived from insect host orders, indicating that the genetic relatedness of B. bassiana strains was highly associated with geographical locality rather than insect host species. The reproductive style of all the B. bassiana populations was found to be non-clonal. Population structure analysis revealed that the average divergent coefficient among populations of B. bassiana was far below 1 (0.1112), which indicated that there was no significant genetic differentiation between populations, and that the overall genetic diversity mainly resulted from the genetic variations within geographical populations. Statistically, genetic distances between populations were positively correlated with geographical distances, suggesting that geographical separation poses an obstacle to the possibility and frequency of genetic exchanges between populations. On the other hand, gene flow was indirectly established to occur between B. bassiana populations. [source] Estrogen Receptor , Gene Polymorphisms and Peak Bone Density in Chinese Nuclear Families,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2003Yue-Juan Qin Abstract PBD is an important determinant of osteoporotic fractures. Few studies were performed to search for genes underlying PBD variation in Chinese populations. We tested linkage and/or association of the estrogen receptor , gene polymorphism with PBD in 401 Chinese nuclear families. This study suggests the ER-, gene may have some minor effects on PBM variation in the Chinese population. Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fractures in the elderly. PBD variation is mainly regulated by genetic factors. Extensive molecular genetics studies have been performed to search for genes underlying PBD variation, largely in whites. Few studies were performed in Chinese populations. In this study, we simultaneously test linkage and/or association of the estrogen receptor , (ER -,) gene polymorphism with PBD in 401 Chinese nuclear families (both parents plus their female children) of 1260 subjects, with the 458 children generally between 20 and 40 years of age. All the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at polymorphic PvuII and XbaI sites inside the ER -, gene. Bone mineral density was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, and intertrochanteric region). Raw bone mineral density values were adjusted by age, height, and weight as covariates. We detected marginally significant results for within-family association (transmission disequilibrium; p = 0.054) between the spine bone mineral density variation and the ER -, XbaI genotypes. For the hip bone mineral density variation, significant (p < 0.05) linkage results were generally found for the two intragenic markers. Analyses of the haplotypes defined by the two markers confer further evidence for linkage of the ER -, with the hip PBD variation. In conclusion, this study suggests that the ER -, gene may have minor effects on PBD variation in our Chinese population. [source] Rapid PCR-RFLP Method for the Identification of 5 Billfish SpeciesJOURNAL OF FOOD SCIENCE, Issue 4 2005Hung-Sheng Hsieh ABSTRACT: A rapid and reliable polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed to identify billfish species Xiphias gladius (swordfish), Makaira nigricans (blue marlin), Makaira indica (black marlin), Istiophorus platypterus (sailfish), and Tetrapturus audax (striped marlin). After DNA extraction and amplifying, the 348-bp PCR products from gene encoding of cytochrome b were subjected to restriction enzyme analysis. No single enzyme tested was able to distinguish the 5 species at the same time, but the combination of results obtained from the digests of Bsa JI and Cac 81 could be used to differentiate the 5 billfish species. This sensitive, rapid, and valid method can be used to detect fraudulent substitutes. [source] Influence of cancer-related gene polymorphisms on clinicopathological features in colorectal cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2008Gen Yoshiya Abstract Background and Aim:, Single nucleotide polymorphisms (SNP) are shown to be related with cancer incidence. It has been reported that CCND1, p21cip1DCC, MTHFR, and EXO1 are related with the risk of malignant neoplasm, but few studies have mentioned the prognosis of the patients. We investigated the SNP of patients and related this to clinicopathological features, including survival rate. Method:, DNA from the tissues of primary colorectal cancer was obtained from surgical resections of 114 patients (68 males and 46 females, 29,83 years). The CCND1 polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and those of other genes were investigated by the TaqMan method. The polymorphisms obtained were statistically analyzed for the relationship with clinicopathological features. Results:, The CG + GG allele was more invasive than the CC allele in histological tumor depth in the DCC codon 201 (P = 0.0086). The 677TT allele in MTHFR had a larger tumor size than the 677CC allele (P = 0.028). In EXO1 P757L polymorphism, patients with the TT allele had a statistically reduced survival rate compared with the other alleles. In CCND1 polymorphisms, we found no statistical significance in clinicopathological features. Conclusions:, From these preliminary data, these polymorphisms would be candidates predicting the clinicopathological features of colorectal cancer, but further more systematic gene analyses are warranted. [source] A community-derived outbreak of adenovirus type 3 in children in Taiwan between 2004 and 2005JOURNAL OF MEDICAL VIROLOGY, Issue 1 2008Sui-Yuan Chang Abstract An outbreak of respiratory adenovirus infection in children was observed in northern Taiwan between November 2004 and February 2005. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the serotype(s) of 172 adenovirus isolates in the outbreak period, we found that adenovirus type 3 (Ad3) was the predominant type (87.2%), followed by Ad2 (6.4%), Ad1 (4.1%), Ad7 (1.2%), Ad4 (0.6%), and Ad5 (0.6%). The genotype of Ad3 was analyzed for 15 isolates from the outbreak period by RFLP of the full-length genome. All these isolates belonged to genotype Ad3a2. Compared with the Ad3-infected patients in the baseline period, a significantly higher proportion of Ad3-infected patients in the outbreak period had severe infections (58.0% vs. 40.2%, P,=,0.01), which included bronchopneumonia (28.7%), exudative tonsillitis (24.1%), and tonsillitis (16.1%). Moreover, patients with severe infections were significantly younger than those without (4.10 vs. 8.15 years, P,<,0.001). In summary, our study demonstrated that Ad3 was the predominant serotype responsible for the respiratory adenovirus outbreak in northern Taiwan during 2004,2005 and was associated with severe infections in the outbreak period. J. Med. Virol. 80:102,112, 2008. © 2007 Wiley-Liss, Inc. [source] Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in TaiwanJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2008Ching-Yu Yen Background:, Many single nucleotide polymorphisms (SNPs) have been found to be associated with oral cancer but the biological interactions through SNPs are seldom addressed. In this study, we focused on the joint effect for SNP combinations of four DNA repair genes, X-ray repair cross-complementing groups (XRCCs) 1,4, involved in major cancer-related pathways. Methods:, Single nucleotide polymorphism genotyping was determined using by polymerase chain reaction-restriction fragment length polymorphism in this study (case = 103, control = 98). Different numbers of combinational SNPs with genotypes called the pseudo-haplotypes from these chromosome-wide genes were used to evaluate their joint effect on oral cancer risk. Results:, Except for XRCC2 rs2040639-AG, none of these SNPs was found to individually contribute to oral cancer risk. However, for two combined SNPs, the proportion of subjects with oral cancer was significantly higher in the pseudo-haplotype with AG-CC genotypes in rs2040639-rs861539 (XRCC2,XRCC3) compared with those with non-AG-CC genotypes. Similarly, the pseudo-haplotype of rs2040639,rs861539,rs2075685 (XRCC2,XRCC3,XRCC4) and rs2040639,rs861539,rs2075685,rs1799782 (XRCCs 1,4) with specific genotype pattern (AG-CC-TG and CT-AG-CC-TG) among three and four combinational SNPs were significantly associated with oral cancer. After controlling for age, gender, smoking, drinking, and betel nut chewing, the estimated odds ratio of oral cancer were 2.45, 5.03, and 10.10 for two, three and four specific SNP combinations, respectively, comparing these specific pseudo-haplotypes to their corresponding non-pseudo-haplotypes. Conclusion:, We have identified the potential combined XRCCs 1,4 SNPs with genotypes that were associated with oral cancer risk and may have an impact on identification of a high-risk population. [source] Association Between Personality Traits and ALDH2 Polymorphism in Japanese Male AlcoholicsALCOHOLISM, Issue 5 2009Mitsuru Kimura Background:, Alcoholics who have developed alcoholism despite a strong negative risk factor, that is, the inactive form of aldehyde dehydrogenase-2 (ALDH2), are considered advantageous for studying predisposing factors for alcoholism. This study aimed to compare personality profiles and clinical characteristics between alcoholics with active and inactive ALDH2. Methods:, Subjects were 460 male Japanese alcoholics hospitalized in Kurihama Alcoholism Center. All patients underwent Cloninger's Tridimensional Personality Questionnaire and semi-structured interviews 4 to 8 weeks after admission to obtain data on personalities and clinical characteristics. ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Sixty-six patients had the inactive form of ALDH2 (ALDH2*1/2*2) and 394 had the active form (ALDH2*1/2*1). Results:, Alcoholics with inactive ALDH2 had significantly higher novelty-seeking (NS) and lower harm-avoidance (HA) scores compared with those with active ALDH2. The inactive ALDH2 group experienced delirium tremens significantly less frequently than the active ALDH2 group. Conclusions:, These results suggest that high NS and low HA scores in alcoholics with inactive ALDH2 are associated with an increased risk for developing alcoholism, despite a low enzymatic ability to eliminate toxic acetaldehyde in these subjects. A study of alcoholics with inactive ALDH2 is useful for detecting environmental or personality factors related to alcoholism. [source] Single nucleotide polymorphism of the MxA gene promoter influences the response to interferon monotherapy in patients with hepatitis C viral infectionJOURNAL OF VIRAL HEPATITIS, Issue 3 2004F. Suzuki Summary. The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2,,5, oligoadenylate synthetase, dsRNA-activated protein kinase and MxA protein. Among these, MxA protein is assumed to be the most specific surrogate parameter for IFN action. This study was performed to elucidate whether a single nucleotide polymorphism (SNP) (G/T at nt-88) in the promoter region of the MxA gene influences the response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection. Polymorphisms of the MxA gene in 235 HCV patients were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequency of SNP was compared between sustained-responders (n = 78) and nonresponders (n = 157), as determined by biochemical and virological responses to IFN. Multivariate analysis showed that among all patients, HCV genotype, HCV RNA level and the SNP of the MxA gene were independent and significant determinants of the outcome of IFN therapy [odds ratio 3.8 (95% confidence interval 2.0,7.0), P < 0.0001; 0.27 (0.15,0.50), P < 0.0001; 1.8 (1.0,3.4), P = 0.0464, respectively]. Furthermore, among patients with a low viral load (,2.0 Meq/mL), MxA-T-positive patients were more likely to show a sustained response compared with MxA-T-negative patients [2.87 (1.3,6.3); 62%vs 36%; P = 0.0075]. Our findings suggested that the SNP of the MxA gene is one of the important host factors that independently influences the response to IFN in patients with chronic HCV infection, especially those with a low viral load. [source] A set of primers for amplification of mitochondrial DNA in Picea abies and other conifer speciesMOLECULAR ECOLOGY RESOURCES, Issue 4 2002S. Jeandroz Abstract Thirteen primer pairs generating intraspecific length and/or presence-absence polymorphism in Picea abies have been obtained from a P. abies mtDNA library, using different methodologies (agarose gel electrophoresis, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation (SSCP). Poly-morphism tests were extended successfully to other Picea species (P. omorika, P. engelmanii and P. glauca) and species belonging to other conifer genera (Abies alba, Larix laricina and Pinus pinaster). This set of PCR-based mitochondrial markers can provide promising tools for studying phylogeography or phylogeny in P. abies and other conifer species in which the mt genome is generally the only one to be transmitted via the female gamete. [source] Lack of association between IRF6 polymorphisms (rs2235371 and rs642961) and non-syndromic cleft lip and/or palate in a Brazilian populationORAL DISEASES, Issue 2 2010LMR Paranaíba Oral Diseases (2010) 16, 193,197 Background:, Interferon regulatory factor 6 (IRF6) gene has emerged as a potential susceptibility gene for non-syndromic cleft lip and/or palate (NSCL/P) in different populations. The aim of this study was to determine the association of IRF6 rs2235371 and rs642961 polymorphisms with NSCL/P in a Brazilian population. Methods:, Two hundred and twenty-eight patients affected by NSCL/P and 126 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results:, Overall genotype distributions of rs2235371 and rs642961 polymorphisms were as expected by Hardy-Weinberg equilibrium test. The rs2235371 polymorphic genotype GA was identified in 10.1% of the patients with NSCL/P and in 10.3% of the control group, revealing no statistical difference. Similarly, the frequency of rs642961 minor genotypes (GA and AA) was quite similar between control group (28.6%) and NSCL/P group (25.4%), without significant difference. Conclusion:, Our findings are consistent with a lack of involvement of IRF6 rs2235371 and rs642961 polymorphisms in the NSCL/P pathogenesis in the Brazilian population. [source] Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workersAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 10 2008Ilker Ates PhD Abstract Background Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). An additional goal was to observe whether these cytokine gene polymorphisms influence the development risk and severity of. Methods Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results TNFA (,238) gene polymorphism principally affected CWP development and severity (OR,=,3.47: 95% CI, 1.12,10.77 and OR,=,4.30: 95% CI, 1.25,14.74, respectively) and also risk of CWP (OR,=,3.79: 95% CI, 1.37,10.46). The TNFA (,308) variant was associated with a risk for the CWP severity (OR,=,2.84: 95% CI, 1.08,7.39). A protective effect of IL6 was found on the development (OR,=,0.48: 95% CI, 0.21,0.93) and severity of CWP (OR,=,0.37: 95% CI, 0.15,0.91). Conclusions We suggest that TNFA (,238) variant may be a risk factor in both development and the severity of CWP, while TNFA (,308) variant seems to be important only in disease severity. On the other hand, IL6 variant may have a protective effect on the development and disease severity. Am. J. Ind. Med. 51:741,747, 2008. Published 2008 Wiley-Liss, Inc. [source] Lack of association between polymorphisms in p53 gene and spermatogenetic failure in a Chinese populationANDROLOGIA, Issue 6 2007N. X. Lu Summary Although various genetic factors have been demonstrated in human male infertility, many genetic causes involving gene variants for the idiopathic male infertility have not yet been elucidated. P53 gene is involved in the meiosis of the male rat and mice, which suggested that p53 plays a critical role in spermatogenesis. To examine whether the codon72 polymorphism and IVS7 + 72C>T polymorphism of the human p53 gene are associated with spermatogenetic failure in Han-Chinese population. A case,control study was conducted with 198 idiopathic infertile patients with nonobstructive azoospermia or severe oligozoospermia and 233 fertile controls. We genotyped the two polymorphisms, codon72 and IVS7 + 72C>T, using polymerase chain reaction-restriction fragment length polymorphism assay. The polymorphisms were identified in both infertile patients and fertile controls. The allele and genotype frequencies of the two polymorphisms were not significantly different between the patients and controls. Further analysis showed that there was no statistically significant difference in the haplotype distributions between the patients and controls. The results of this study suggest that the codon72 and IVS7 + 72C>T polymorphisms of the p53 gene are unlikely to contribute to the pathogenesis of idiopathic male infertility with spermatogenetic failure. [source] Identification of ovalbumin phenotypes of the Asian indigenous chicken populations using polymerase chain reaction-restriction fragment length polymorphismANIMAL SCIENCE JOURNAL, Issue 5 2003Keiji KINOSHITA ABSTRACT Three electrophoretic variations (AA, BB and AB) of ovalbumin controlled by codominant alleles OvA and OvB have been observed in various chicken populations. We compared nucleotide sequences of the open reading frame between two alleles of ovalbumin gene. The difference between the two alleles was found as a non-synonymous substitution of asparagine to aspartic acid as a result of AAT to GAT point mutation at position 8032,8034 in exon 8. We developed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol in combination with Mbo I restriction endnuclease mapping for the detection of this substitution. By the PCR-RFLP the allelic frequency of the OvB was estimated to be within the range of 0.000,0.150 in 11 Asian indigenous chicken populations and 0.000 in four improved breeds used in the present study. Gene frequency, estimated by PCR-RFLP in the present study, paralleled that obtained by protein polymorphisms of egg white. Thus, this study provides, for the first time, information of the occurrence of ovalbumin allele OvA and OvB in Asian indigenous chicken populations. [source] Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian populationBJU INTERNATIONAL, Issue 4 2007Rama D. Mittal OBJECTIVE To explore the association of vitamin-D receptor (VDR) genotypes and haplotypes (variants at the Fok-I, and Taq-I sites) with the risk of bladder cancer, as vitamin D is antiproliferative and reported to induce apoptosis in human bladder tumour cells in vitro. PATIENTS, SUBJECTS AND METHODS A case-control study using polymerase chain reaction-restriction fragment length polymorphism was conducted in 130 patients with bladder cancer and 346 normal healthy individuals in a north Indian population. Patients were also categorized according to grade and stage of tumour. RESULTS There was a significant difference in genotype and allelic distribution of VDR (Fok-I) polymorphism in the patients (P = 0.033 and = 0.017, respectively). The FF genotype was associated with twice the risk for bladder cancer (odds ratio 2.042, 95% confidence interval, CI, 0.803,5.193). There was no significant difference in genotypic distribution or allelic frequencies of the VDR (Taq-I) polymorphism (P = 0.477 and 0.230) when compared with the controls. The stage and grade of the bladder tumours had no association with VDR (Fok-I and Taq-I) genotypes. There was a significant difference in the frequency distribution of the haplotypes FT and fT (P < 0.001); these haplotypes had a protective effect in the control group (odds ratio 0.167, 95% CI 0.096,0.291, and 0.079, 0.038,0.164). CONCLUSION These data suggest that VDR (Fok-I) polymorphism is associated with the risk of bladder cancer. Further, the results for the haplotype FT and fT indicate that patients with this haplotype have a lower risk of developing bladder cancer than those with other haplotypes. [source] Large-scale Analysis of Mutations in RET Exon 16 in Sporadic Medullary Thyroid Carcinomas in JapanCANCER SCIENCE, Issue 6 2001Torn Takano Germline mutations in the RET proto-oncogene are the cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (MTC) have also been reported to have mutations in the RET gene. However, two previous reports have given discrepant results on the frequency of the mutations in RET in sporadic MTCs in Japan. To clarify this problem, we analyzed mutations in RET exon 16 in 72 sporadic MTCs by means of the two methods used in the previous studies, direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutations in exon 16 were detected in only 2 of 72 cases of sporadic MTC. These results suggest that when a MTC has a mutation in RET exon 16, it is more likely to be a hereditary MTC than a sporadic one in Japan. [source] Impact of leptin and leptin-receptor gene polymorphisms on serum lipids in Japanese obese childrenACTA PAEDIATRICA, Issue 8 2010T Okada Abstract Aim:, Leptin is one of the factors affecting serum lipid profile. We investigated the association between serum lipids and leptin/leptin receptor (LEPR) gene polymorphisms in obese Japanese children. Methods:, One hundred and thirty-six obese children (99 males and 37 females, relative weight over than 20%) from 5 to 17 years of age were recruited from 10 institutes. Four known polymorphisms in leptin gene [(+19)A G, (,2548)G A, (,188)C A, (,633)C T] and four known polymorphisms in LEPR gene [Lys109Arg, Gln223Arg, Pro(G)1019Pro(A), Ser(T)343Ser(C)] were determined using polymerase chain reaction-restriction fragment length polymorphism-based analyses. Results:, No associations were found between leptin gene polymorphisms and serum lipid profile. On the other hand, Lys109Arg and Ser343Ser polymorphism in LEPR gene, but not Gln223Arg or Pro1019Pro, had significant relationships with serum lipid profile; lower total and low-density lipoprotein cholesterol levels in Arg109Arg homozygotes, and lower TG levels in Ser343Ser(C/C) homozygotes. In addition, LEPR gene also associated with relative weight; Arg109Arg homozygotes had higher relative weight and Ser343Ser(C/C) homozygotes had lower one. Conclusion:, These results suggest that LEPR gene polymorphisms may partly contribute to serum lipid profile in obese children. [source] Association of the SULT1A1 R213H polymorphism with colorectal cancerCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2002Chung Fai Wong Summary 1.,Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild-type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N -OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer. 2.,Genotyping, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis. 3.,Examination of the sulphonating ability of the two allozymes with respect to the substrates p -nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence. 4.,From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population. [source] Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseasesINFLAMMATORY BOWEL DISEASES, Issue 1 2006Marie Pierik MD Abstract Background: Evidence that a deficient innate immune response toward the bacterial flora of the gut plays a role in the pathogenesis of inflammatory bowel disease (IBD) is growing. This is underscored by the finding of the association between CARD15 variants and Crohn's disease (CD) and D299G in Toll-like receptor (TLR) 4 and IBD. Our aims were to study nonsynonymous polymorphisms in other TLR genes in IBD. Methods: Thirty-five single nucleotide polymorphisms (SNP) in TLR1-10 were identified from public databases. 284 IBD parent-child trios and a second independent cohort of 285 IBD patients and 191 healthy controls were genotyped with polymerase chain reaction-restriction fragment length polymorphisms. Patients were pooled for genotype-phenotype analyses. Results: Although none of the SNPs was involved in disease susceptibility, a number of variants influenced the disease phenotype. A positive association between TLR1 R80T and pancolitis in UC (P = .045, OR [95% CI] 2.844 [1.026-7.844]) was found. The TLR2 R753G SNP was also associated with pancolitis (P = .027, OR [95% CI] 4.741 [1.197-18.773]). The relative risks for heterozygous patients to develop pancolitis were 5.8 and 3.3 for R80T and R753G, respectively. There was a negative association between TLR6 S249P and ulcerative colitis with proctitis only (P = .026, OR [95% CI] 0.223 [0.096-0.705]). In CD, we found a negative association between ileal disease involvement and TLR1 S602I (P = .03, OR [95% CI] 0.522 [0.286-0.950]). Conclusion:TLR2 and its cofactors TLR1 and TLR6 are involved in the initial immune response to bacteria by recognizing peptidoglycan. An association between nonsynonymous variants in the TLR1, - 2, and - 6 genes and extensive colonic disease in UC and CD was found. Our findings further highlight the role of an abnormal innate immune response in the pathogenesis of IBD. [source] | ||||||||||||||||||||||