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对中国汉族人群妊娠期糖尿病病例对照样本中 HKDC1 ，BACE2 ，SLC16A11 和 TMEM163 SNPs 的先前全基因组关联研究的复制
Authors Tan YX, Hu SM, You YP, Yang GL, Wang W
Received 27 February 2019
Accepted for publication 13 May 2019
Published 27 June 2019 Volume 2019:12 Pages 983—989
DOI https://doi.org/10.2147/DMSO.S207019
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Professor Ming-Hui Zou
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 HKDC 1 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, HKDC 1 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); HKDC 1 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 HKDC 1 with glucose metabolism remained statistically significant. The A allele of TMEM163 rs998451 was not detected in this population.
Conclusion: HKDC 1 rs4746822, BACE2 rs6517656 and SLC16A11 rs13342232 are associated with glucose metabolism in pregnant women of Han Chinese.
Keywords: gestational diabetes mellitus, SLC16A11, HKDC1, BACE2, TMEM163
