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Tag Single Nucleotide Polymorphisms (tag + single_nucleotide_polymorphism)
Selected AbstractsInvestigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetesDIABETIC MEDICINE, Issue 8 2008D. Currie Abstract Aims Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene. Methods Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies. Results ,2 analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case,control collection negated this association. Conclusions We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes. [source] A new multimarker test for family-based association studiesGENETIC EPIDEMIOLOGY, Issue 1 2007Cyril S. Rakovski Abstract We propose a new multimarker test for family-based studies in candidate genes. We use simulations under different genetic models to assess the performance of competing testing strategies, characterized in this study as combinations of the following important factors: genes, statistical tests, tag single nucleotide polymorphisms (SNP) methods, number of tag SNPs and family designs. An ANOVA model is employed to provide descriptive summaries of the effects on power of the above-mentioned factors. We find that tag SNP methods, gene characteristics and family designs have minimal impact on the best testing strategy. The familywise error rate (FWER) controlling multiple comparison procedure and the new multimarker test offer the highest power followed by the asymptotic global haplotype test. Both the FWER and the multimarker test are invariant to family designs and gain power as we increase the number of tag SNPs. However, the performance of the global haplotype test is slightly degraded when analyzing larger numbers of tag SNPs. Within the framework of our study, the best strategy for family-based studies in candidate genes that emerged from our analysis is to use the FWER or the multimarker test and select 6,10 tag SNPs using any of the tag SNP methods considered. We confirm the conclusions of our study with an application to Alzheimer's disease data. Genet. Epidemiol. © 2006 Wiley-Liss, Inc. [source] The influence of common gene variants of the xenobiotic receptor (PXR) in genetic susceptibility to intrahepatic cholestasis of pregnancyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010G. CASTAÑO Aliment Pharmacol Ther,31, 583,592 Summary Background, The xenobiotic nuclear pregnane X receptor is implicated in many physiological pathways and diseases, including bile acid detoxification and cholestasis. Aim, To estimate the contribution of common gene variants of the xenobiotic receptor (pregnane X receptor, PXR) to genetic susceptibility to intrahepatic cholestasis of pregnancy. Methods, A total of 101 intrahepatic cholestasis of pregnancy patients and 171 healthy pregnant women in the third trimester of their pregnancies were included. Four tag single nucleotide polymorphisms (SNPs) (rs12488820 C/T, rs2472671 C/T, rs2461823 A/G, and rs1054191 A/G) encompassing 36 kb in chromosome 3, with a minor allele frequency ,0.10 and representing 33 polymorphic sites were genotyped. Besides these, three additional SNPs (rs3814057, rs6785049, and rs7643645) were included because they showed previous evidence of functionality. Results, Genotypic test for single SNPs showed that rs2461823 genotypes were significantly associated with intrahepatic cholestasis of pregnancy (P < 0.0069), OR per G allele: 1.44, 95% CI: 1.01,2.05, P < 0.042. The Cochran-Armitage test for trend and the allelic test showed a significant association with disease status (P < 0.04 and 0.03 respectively), G being the risk allele. A positive association between rs2461823 and ALT, AST, and bilirubin concentrations was observed. Neonate birth weight adjusted by the Capurro index was significantly associated with rs2461823 (P < 0.05); the proportion of the total variation attributed to rs2461823 genotypes was 7.8%. Conclusion, Common PXR polymorphisms may contribute to the genetic susceptibility to intrahepatic cholestasis of pregnancy. [source] SERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibilityCANCER, Issue 18 2010Hyoungseok Ju PhD Abstract BACKGROUND: A primary inhibitor of plasminogen activators, SERPINE1 (serpin peptidase inhibitor 1, clade E, member 1, also known as plasminogen activator inhibitor type 1), is an important regulator in tumorigenesis and is highly expressed in many cancers. METHODS: Five tag single nucleotide polymorphisms (SNPs) and 1 insertion polymorphism within SERPINE1 were genotyped in 1101 unrelated Korean individuals (a case group of 612 patients with gastric cancer and a control group of 489 healthy individuals). Associations with susceptibility to diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer were assessed using multivariate logistic regression analyses adjusted for age and sex. Allelic differences in the contribution to gene expression were measured using luciferase assays. RESULTS: SNP c.1162+162C>T (rs2227692) in intron 7 was associated with susceptibility to DGC but not with susceptibility to intestinal-type gastric cancer. The minor allele-carrying genotypes C/T and T/T had 1.6-fold greater odds of DGC than the C/C genotype (P = .00084). This SNP was linked to a repeat-number variation c.1162+604AAAG(11_17), a deletion (del) variation c.1162+664_1162+673del, and another SNP c.1162+859T>A (rs2070683) in intron 7 based on the sequencing of 5 patients and 5 controls. The risk haplotype of the 4 variations exhibited a 30% greater gene expression level than the nonrisk haplotype in luciferase reporter assays (P = .025). In contrast, DGC susceptibility was not associated with the c.,1969_,1968insG polymorphism (rs1799768) in the promoter, commonly known as 4G/5G, in which the minor 5G allele is less active in transcription than the major 4G allele. CONCLUSIONS: An association between SERPINE1 and DGC susceptibility was observed with 4 correlated polymorphisms in intron 7 rather than the 4G/5G polymorphism in the promoter, although all polymorphisms affected gene expression. Cancer 2010. © 2010 American Cancer Society. [source] | ||||||||||