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Replication of previous genome-wide association studies of HKDC1, BACE2, SLC16A11 and TMEM163 SNPs in a gestational diabetes mellitus case-control sample from Han Chinese population.

ABSTRACT: Background: Four novel glucose metabolism risk loci (HKDC1 rs4746822, BACE2 rs6517656, SLC16A11 rs13342232 and TMEM163 rs998451) were identified in recent genome-wide association studies (GWAS) of Afro-Caribbean, European, Hispanic, Thai, Mexican, Latin American and Indian populations. None of the abovementioned SNPs has been reported in a Han Chinese population. Aim: To replicate the relationships between HKDC1 rs4746822, BACE2 rs6517656, SLC16A11 rs13342232 and TMEM163 rs998451 with gestational diabetes mellitus (GDM) in a Han Chinese population. Methods: This was a case-control study which enrolled 334 pregnant women with GDM and 367 pregnant women with normal glucose tolerance. The linear regression and logistic regression were used to estimate the association between SNPs with the risk of GDM, HOMA-IR and fasting insulin levels. The fasting insulin concentration and HOMA-IR were log10 transformed before analysis. Results: No significant differences in the alleles and genotypes of SLC16A11 rs13342232, HKDC1 rs4746822 and BACE2 rs6517656 were observed between cases and controls. After adjusting the weekly BMI growth, pre-pregnancy BMI and maternal age, under the additive model, SLC16A11 rs13342232 was associated with log10fasting serum insulin (Beta=0.046, p=0.016), log10HOMA-IR level (Beta=0.061, p=0.003) and fasting plasma glucose level (Beta=0.164, p=0.011); HKDC1 rs4746822 was associated with OGTT 2-hr plasma glucose level (Beta=0.239, p=0.016); and BACE2 rs6517656 was associated with log10fasting serum insulin (Beta=-0.053, p=0.044) and log10HOMA-IR level (Beta=-0.060, p=0.048). After correction for multiple testing, the associations of SLC16A11 and HKDC1 with glucose metabolism remained statistically significant. The A allele of TMEM163 rs998451 was not detected in this population. Conclusion: HKDC1 rs4746822, BACE2 rs6517656 and SLC16A11 rs13342232 are associated with glucose metabolism in pregnant women of Han Chinese.

SUBMITTER: Tan YX

PROVIDER: S-EPMC6602052 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Replication of previous genome-wide association studies of HKDC1, BACE2, SLC16A11 and TMEM163 SNPs in a gestational diabetes mellitus case-control sample from Han Chinese population.

Tan Yi-Xiong YX Hu Shi-Min SM You Yi-Ping YP Yang Gui-Lian GL Wang Wei W

Diabetes, metabolic syndrome and obesity : targets and therapy 20190627

Background: Four novel glucose metabolism risk loci (HKDC1 rs4746822, BACE2 rs6517656, SLC16A11 rs13342232 and TMEM163 rs998451) were identified in recent genome-wide association studies (GWAS) of Afro-Caribbean, European, Hispanic, Thai, Mexican, Latin American and Indian populations. None of the abovementioned SNPs has been reported in a Han Chinese population. Aim: To replicate the relationships between HKDC1 rs4746822, BACE2 rs6517656, ...[more]

PMID: 31417298

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Project description:BackgroundGestational diabetes mellitus (GDM) affects the metabolism of both the mother and fetus during and after pregnancy. Genetic factors are important in the pathogenesis of GDM, and associations vary by ethnicity. However, related studies about the relationship between the susceptibility genes and glucose traits remain limited in China. This study aimed to identify genes associated with GDM susceptibility in Chinese Han women and validate those findings using clinical data during pregnancy and postpartum period.MethodsA genome-wide association study (GWAS) of 398 Chinese Han women (199 each with and without GDM) was conducted and associations between single nucleotide polymorphisms (SNPs) and glucose metabolism were identified by searching public databases. Relationships between filtered differential SNPs and glucose metabolism were verified using clinical data during pregnancy. The GDM group were followed up postpartum to evaluate the progression of glucose metabolism.ResultsWe identified five novel SNPs with genome-wide significant associations with GDM: rs62069863 in TRPV3 gene and rs2232016 in PRMT6 gene were positive correlated with 1 h plasma glucose (1hPG) and 2 h plasma glucose (2hPG), rs1112718 in HHEX/EXOC6 gene and rs10460009 in LPIN2 gene were positive associated with fasting plasma glucose, 1hPG and 2hPG, rs927316 in GLIS3 gene was negative correlated with 2hPG. Of the 166 GDM women followed up postpartum, rs62069863 in TRPV3 gene was positively associated with fasting insulin, homoeostasis model assessment of insulin resistance.ConclusionsThe variants of rs62069863 in TRPV3 gene, rs2232016 in PRMT6 gene, rs1112718 in HHEX/EXOC6 gene, rs927316 in GLIS3 gene, and rs10460009 in LPIN2 gene were newly-identified susceptibility loci for GDM in the Chinese Han population. TRPV3 was associated with worse insulin resistance postpartum.Trial registrationThis study was registered in the Chinese Clinical Trial Registry.Trial registration numberChiCTR2100043762. Date of first registration: 28/02/2021.

Dataset Information

Replication of previous genome-wide association studies of HKDC1, BACE2, SLC16A11 and TMEM163 SNPs in a gestational diabetes mellitus case-control sample from Han Chinese population.

Publications

Replication of previous genome-wide association studies of <i>HKDC1, BACE2, SLC16A11</i> and <i>TMEM163</i> SNPs in a gestational diabetes mellitus case-control sample from Han Chinese population.

Similar Datasets

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