Genome-wide Analysis Study of Gestational Diabetes Mellitus and Related Pathogenic Factors in a Chinese Han Population

Overview

Journal BMC Pregnancy Childbirth

Publisher Biomed Central

Specialty Gynecology & Obstetrics

Date 2023 Dec 13

PMID 38087213

Authors

Shufan Yue

Ling Pei

Fenghua Lai

Huangmeng Xiao

Zeting Li

Rui Zeng

Li Chen

Wenzhan Chen

Huiling Liu

Yanbing Li

Haipeng Xiao

Xiaopei Cao

Affiliations

Soon will be listed here.

Abstract

Background: Gestational 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.

Methods: A 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.

Results: We 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.

Conclusions: The 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 Registration: This study was registered in the Chinese Clinical Trial Registry.

Trial Registration Number: ChiCTR2100043762. Date of first registration: 28/02/2021.

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References

He S, Ji D, Liu Y, Deng X, Zou W, Liang D . Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-β among women with polycystic ovary syndrome: a cross-sectional study. J Assist Reprod Genet. 2023; 40(8):1983-1993. PMC: 10371916. DOI: 10.1007/s10815-023-02843-7. View

Park S, Liu M, Kang S . Alcohol Intake Interacts with CDKAL1, HHEX, and OAS3 Genetic Variants, Associated with the Risk of Type 2 Diabetes by Lowering Insulin Secretion in Korean Adults. Alcohol Clin Exp Res. 2018; 42(12):2326-2336. DOI: 10.1111/acer.13888. View

Israel E, Lasky-Su J, Markezich A, Damask A, Szefler S, Schuemann B . Genome-wide association study of short-acting β2-agonists. A novel genome-wide significant locus on chromosome 2 near ASB3. Am J Respir Crit Care Med. 2015; 191(5):530-7. PMC: 4384768. DOI: 10.1164/rccm.201408-1426OC. View

Wang C, Tong M, Zhang J, Yu J, Meng W, Jin L . Prevalence of gestational diabetes mellitus and its determinants among pregnant women in Beijing. J Matern Fetal Neonatal Med. 2020; 35(7):1337-1343. DOI: 10.1080/14767058.2020.1754395. View

Li Z, Cheng Y, Wang D, Chen H, Chen H, Ming W . Incidence Rate of Type 2 Diabetes Mellitus after Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of 170,139 Women. J Diabetes Res. 2020; 2020:3076463. PMC: 7204113. DOI: 10.1155/2020/3076463. View

Zhang X, Zhao X, Huo L, Yuan N, Sun J, Du J . Risk prediction model of gestational diabetes mellitus based on nomogram in a Chinese population cohort study. Sci Rep. 2020; 10(1):21223. PMC: 7718223. DOI: 10.1038/s41598-020-78164-x. View

Watanabe N, Hiramatsu K, Miyamoto R, Yasuda K, Suzuki N, Oshima N . A murine model of neonatal diabetes mellitus in Glis3-deficient mice. FEBS Lett. 2009; 583(12):2108-13. DOI: 10.1016/j.febslet.2009.05.039. View

Huang Y, Heist R, Chirieac L, Lin X, Skaug V, Zienolddiny S . Genome-wide analysis of survival in early-stage non-small-cell lung cancer. J Clin Oncol. 2009; 27(16):2660-7. PMC: 2690391. DOI: 10.1200/JCO.2008.18.7906. View

Yang Y, Chang B, Samson S, Li M, Chan L . The Krüppel-like zinc finger protein Glis3 directly and indirectly activates insulin gene transcription. Nucleic Acids Res. 2009; 37(8):2529-38. PMC: 2677877. DOI: 10.1093/nar/gkp122. View

10.

Permana S, Lukman H, Norahmawati E, Eka Puspita O, Faisal Moh Al Zein D, Kawamoto Y . East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population. Acta Biochim Pol. 2019; 66(2):679-686. DOI: 10.18388/abp.2020_5563. View

11.

Metzger B, Lowe L, Dyer A, Trimble E, Chaovarindr U, Coustan D . Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008; 358(19):1991-2002. DOI: 10.1056/NEJMoa0707943. View

12.

Choi S, Jeong H, Kim H, Choi D, Cho S, Seong J . Skeletal muscle-specific Prmt1 deletion causes muscle atrophy via deregulation of the PRMT6-FOXO3 axis. Autophagy. 2019; 15(6):1069-1081. PMC: 6526864. DOI: 10.1080/15548627.2019.1569931. View

13.

Sudmant P, Rausch T, Gardner E, Handsaker R, Abyzov A, Huddleston J . An integrated map of structural variation in 2,504 human genomes. Nature. 2015; 526(7571):75-81. PMC: 4617611. DOI: 10.1038/nature15394. View

14.

Ahn M, Won H, Lee J, Lee S, Sun J, Park Y . The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations. Hum Genet. 2011; 131(3):365-72. DOI: 10.1007/s00439-011-1080-z. View

15.

Jackson J, Nutt S, McCormack M . The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease. Front Immunol. 2023; 14:1197490. PMC: 10313424. DOI: 10.3389/fimmu.2023.1197490. View

16.

Wen X, Yang Y . Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes. J Mol Endocrinol. 2016; 58(2):R73-R85. DOI: 10.1530/JME-16-0232. View

17.

Cheng Y, Gao Z, Zhang T, Wang Y, Xie X, Han G . Decoding mA RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance. Cell Stem Cell. 2022; 30(1):69-85.e7. DOI: 10.1016/j.stem.2022.12.003. View

18.

Metzger B, Gabbe S, Persson B, Buchanan T, Catalano P, Damm P . International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33(3):676-82. PMC: 2827530. DOI: 10.2337/dc09-1848. View

19.

Sun X, Sun H, Li P . Association of circulating inflammatory cells and platelets with gestational diabetes and pregnancy outcomes. Clin Chim Acta. 2021; 523:87-96. DOI: 10.1016/j.cca.2021.09.004. View

20.

Sawatani T, Kaneko Y, Doutsu I, Ogawa A, Ishikawa T . TRPV2 channels mediate insulin secretion induced by cell swelling in mouse pancreatic β-cells. Am J Physiol Cell Physiol. 2019; 316(3):C434-C443. DOI: 10.1152/ajpcell.00210.2017. View