Dataset Information

Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study.

ABSTRACT: BACKGROUND: Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian subjects. METHODS: Single nucleotide polymorphisms (SNPs) of SLC30A8; rs7002176, rs1995222 and rs13266634 were genotyped in 1140 T2D and 973 non-diabetic control subjects. Of these, 33 GADA positive diabetic subjects and 353 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. RESULTS: The recessive genetic model controlled for age, race, gender and BMI shows that the alternative SLC30A8 variant, rs1995222 is associated with GADA negative diabetes (OR?=?1.29, P?=?0.02) in Malaysian subjects. The most common variant, rs13266634 is also associated with GADA negative diabetes (OR?=?1.45, P?=?0.001). This association is more pronounced among Malaysian Indians (OR?=?1.93, P?=?0.001). Moreover, the CG haplotype and CG-CG diplotype have been equally associated with increased diabetic risk (OR?=?1.67, P?=?8.6?×?10-5). CONCLUSIONS: SLC30A8 SNPs and haplotypes are associated with GADA negative diabetes in Malaysian subjects, and this association is markedly higher among Malaysian Indian subjects.

SUBMITTER: Salem SD

PROVIDER: S-EPMC3893602 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study.

Salem Sameer D SD Saif-Ali Riyadh R Ismail Ikram S IS Al-Hamodi Zaid Z Muniandy Sekaran S

BMC endocrine disorders 20140106

<h4>Background</h4>Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarbox ...[more]

PMID: 24393180

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Project description:Common PCSK1 variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common PCSK1 variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI (P?=?0.006) and obesity (P?=?0.018) but also increased the obesity incidence during the 20 years of follow-up (HR?=?1.53 [1.07-2.19], P?=?0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI (P?=?0.028) and obesity (P?=?0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR?=?1.23 [1.05-1.45], P?=?9.5×10(-3)). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI (P?=?4.2×10(-3)) and obesity (P?=?3.4×10(-3)) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group (P?=?0.756 and P?=?0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full PCSK1 locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results suggest that the association of rs6232 with obesity may be age-dependent in European-Americans. However, multiple replication studies in multi-ethnic American population are needed to confirm our findings.

Project description:Background and objectivesPotassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.MethodsA case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies.ResultsKCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.ConclusionKCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.

Dataset Information

Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study.

Publications

Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study.

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