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Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.

ABSTRACT: To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women.In this study, 1764 unrelated pregnant women were recruited, of which 725 women had GDM and 1039 served as controls. Six single nucleotide polymorphisms (rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK) were genotyped using TaqMan allelic discrimination assays. The genotype and allele distributions of each SNP between the GDM cases and controls and the combined effects of alleles for the risk of developing GDM were analyzed. We found that the rs4402960, rs2383208 and rs391300 were statistically associated with GDM (OR?=?1.207, 95%CI?=?1.029-1.417, p?=?0.021; OR?=?1.242, 95%CI?=?1.077-1.432, p?=?0.003; OR?=?1.202, 95%CI?=?1.020-1.416, P?=?0.028, respectively). In addition, the effect was greater under a recessive model in rs391300 (OR?=?1.820, 95%CI?=?1.226-2.701, p?=?0.003). Meanwhile, the joint effect of these three loci indicated an additive effect of multiple alleles on the risk of developing GDM with an OR of 1.196 per allele (p?=?1.08×10(-4)). We also found that the risk alleles of rs2383208 (b?=?-0.085, p?=?0.003), rs4402960 (b?=?-0.057, p?=?0.046) and rs10830963 (b?=?-0.096, p?=?0.001) were associated with HOMA-B, while rs7754840 was associated with decrease in insulin AUC during a 100 g OGTT given at the time of GDM diagnosis (b?=?-0.080, p?=?0.007).Several risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. The effects of these SNPs on GDM might be through the impairment of beta cell function and these risk loci contributed additively to the disease.

SUBMITTER: Wang Y

PROVIDER: S-EPMC3214026 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.

Wang Ying Y Nie Min M Li Wei W Ping Fan F Hu Yingying Y Ma Liangkun L Gao Jinsong J Liu Juntao J

PloS one 20111111 11

<h4>Background</h4>To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women.<h4>Methodology/principal findings</h4>In this study, 1764 unrelated pregnant women were recruited, of which 725 women had GDM and 1039 served as controls. Six single nucleotide polymorphisms (rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1 ...[more]

PMID: 22096510

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Project description:BackgroundThis study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM).MethodsSeventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1-2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively.ResultsThe risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = - 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = - 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e-11). All analyses were adjusted for age, body mass index, and ethnicity.ConclusionsThis study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.

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Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.

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Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.

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