Genetic variations of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) are not associated with polycystic ovary syndrome.
ABSTRACT No statistically significant differences in genotype and allele frequencies of single nucleotide polymorphism (SNP) rs13266634 in gene SLC30A8 were found between patients with polycystic ovary syndrome (PCOS) and healthy controls. No associations were observed between genotype of rs13266634 and the quantitative clinical features of PCOS patients in the PCOS group after adjustment for body mass index.
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ABSTRACT: Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing beta-cells, and two linkage disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits.Nature 03/2007; 445(7130):881-5. · 38.60 Impact Factor
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ABSTRACT: Several genome-wide association studies identified a strong association of SLC30A8 with type 2 diabetes in individuals of European ancestry. The effect of the association of rs13266634 with type 2 diabetes or related glycemic traits has not been fully extended to non-European populations, and a comprehensive examination of common variants in the gene has not yet been carried out in Han Chinese. The objective of the study was to investigate the association of SLC30A8 with type 2 diabetes in Chinese. A comprehensive gene-based association study was performed using 14 tagging single-nucleotide polymorphism (SNPs) of SLC30A8 in Han Chinese subjects with normal glucose tolerance (NGT; n = 721), impaired glucose regulation (IGR; n = 375), and type 2 diabetes (n = 521). A significant association for SNP rs13266634 was observed between patients with type 2 diabetes and NGT controls (P = 0.016). The association was also observed between combined type 2 diabetes/IGR and NGT subjects (P = 0.002). The adjusted odds ratios for homozygote CC vs. TT at this locus were 1.71 for type 2 diabetes (95% confidence interval 1.19-2.45, P = 0.002) and 1.77 for type 2 diabetes and IGR (95% confidence interval 1.29-2.42, P = 0.0001). We further studied the genotype-phenotype correlation in 70 Han Chinese using iv glucose tolerance test and found an association between SNP rs13266634 and acute insulin response to glucose and disposition index (adjusted P = 0.012 and 0.004, respectively). Our results provide evidence that SLC30A8 is a susceptible locus for type 2 diabetes in Chinese population, and its variant can influence insulin secretion.Journal of Clinical Endocrinology & Metabolism 10/2008; 93(10):4107-12. · 6.43 Impact Factor
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ABSTRACT: Common variants of the gene encoding transcription factor 7-like 2 (TCF7L2) have a powerful effect on individual risk of type 2 diabetes (per allele odds ratio approximately 1.35). Polycystic ovary syndrome (PCOS) and type 2 diabetes are familial conditions sharing common features. Based on this, the aim of the present study was to establish whether variation in TCF7L2 also influences the development of PCOS. We conducted a genetic association study of variants of TCF7L2 (rs7903146 and rs12255372) using both case-control and quantitative trait approaches. Case-control analyses were conducted in (1) 369 PCOS cases and 2574 controls of UK British/Irish origin, and (2) 540 women with PCOS symptoms and 1083 controls from the Northern Finland Birth Cohort of 1966. Quantitative trait analyses (androgen levels) were also performed (1249 individuals). There was no association between rs7903146 and PCOS in the UK case-control study (Cochran-Armitage test, p = 0.51); nor with symptomatic status in the Finnish cohort (p = 0.36). In addition, there were no relationships between the TCF7L2 single nucleotide polymorphism rs7903146 and androgen levels (UK cases, p = 0.99; Finnish controls, p = 0.57; Finnish symptomatic cases, p = 0.80). Results at rs12255372 were similar, reflecting strong linkage disequilibrium with rs7903146. Our study was powered to detect an effect on PCOS susceptibility similar to that previously reported for these variants on type 2 diabetes. Failure to detect any evident association with PCOS provides the strongest evidence yet that the genetic architecture of these related conditions is qualitatively distinct.Diabetologia 12/2007; 50(11):2318-22. · 6.49 Impact Factor