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The association between HHEX single-nucleotide polymorphism rs5015480 and gestational diabetes mellitus: A meta-analysis.

ABSTRACT: OBJECTIVE:To evaluate the association between the rs5015480 single-nucleotide polymorphism of hematopoietically expressed homeobox (HHEX) and gestational diabetes mellitus (GDM) via meta-analysis. METHODS:A comprehensive electronic search was performed of the PubMed, Springer, Science Direct, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases for studies worldwide on the relationship between HHEX rs5015480 and GDM published up to July 2019. Rigorous inclusion and exclusion criteria were developed, and the quality of studies was assessed using the Newcastle-Ottawa scale, followed by heterogeneity evaluation using the Q test and I statistic and data pooling. A meta-analysis was then performed on the included studies using RevMan 5.3. RESULTS:A total of 4 eligible case-control studies were included, involving a total of 1651 patients and 3513 controls. The meta-analysis showed the following odds ratios: C allele vs T allele, 1.24 (95% confidence interval [CI]: 1.12-1.38); CC genotype vs TT genotype, 1.65 (95% CI: 1.26-2.17); CC genotype vs CT genotype, 1.22 (95% CI: 1.00-1.50); and CC genotype vs CT?+?TT genotype, 1.32 (95% CI: 1.09-1.61). CONCLUSIONS:HHEX rs5015480 represents a risk factor for the development of GDM, and pregnant women carrying the CC genotype have an increased risk of GDM.

SUBMITTER: Wang X

PROVIDER: S-EPMC7220328 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The association between HHEX single-nucleotide polymorphism rs5015480 and gestational diabetes mellitus: A meta-analysis.

Wang Xingjie X Ding Yuanlin Y Zhang Xinshan X Rao Jiawei J Yu Haibin H Pan Haiyan H

Medicine 20200301 12

<h4>Objective</h4>To evaluate the association between the rs5015480 single-nucleotide polymorphism of hematopoietically expressed homeobox (HHEX) and gestational diabetes mellitus (GDM) via meta-analysis.<h4>Methods</h4>A comprehensive electronic search was performed of the PubMed, Springer, Science Direct, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases for studies worldwide on the relationship between HHEX rs5015480 and GDM published up to July 2019. Rigorous inclusi ...[more]

PMID: 32195947

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Project description:Background This 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). Methods Seventy-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. Results The 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. Conclusions This 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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The association between HHEX single-nucleotide polymorphism rs5015480 and gestational diabetes mellitus: A meta-analysis.

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The association between HHEX single-nucleotide polymorphism rs5015480 and gestational diabetes mellitus: A meta-analysis.

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