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Genetic variants associated with beta-cell function and insulin sensitivity potentially influence bile acid metabolites and gestational diabetes mellitus in a Chinese population.

Authors
  • Zhou, Qiulun1
  • Wang, Ying2
  • Gu, Yuqin1
  • Li, Jing3
  • Wang, Hui3
  • Leng, Junhong4
  • Li, Weiqin4
  • Yu, Zhijie5
  • Hu, Gang6
  • Ma, Ronald Ching Wan7, 8
  • Fang, Zhong-Ze9
  • Yang, Xilin10
  • Jiang, Guozhi11
  • 1 School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong, China. , (China)
  • 2 The Second School of Clinical Medicine, Key Laboratory of 3D Printing Technology in Stomatology, Guangdong Medical University, Dongguan, Guangdong, China. , (China)
  • 3 Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China. , (China)
  • 4 Project Office, Tianjin Women and Children's Health Center, Tianjin, China. , (China)
  • 5 Population Cancer Research Program and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. , (Canada)
  • 6 Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
  • 7 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. , (China)
  • 8 Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. , (China)
  • 9 Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China [email protected] [email protected] [email protected] , (China)
  • 10 Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China [email protected] [email protected] [email protected] , (China)
  • 11 School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong, China [email protected] [email protected] [email protected] , (China)
Type
Published Article
Journal
BMJ Open Diabetes Research & Care
Publisher
BMJ
Publication Date
Sep 01, 2021
Volume
9
Issue
1
Identifiers
DOI: 10.1136/bmjdrc-2021-002287
PMID: 34518156
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To investigate associations between genetic variants related to beta-cell (BC) dysfunction or insulin resistance (IR) in type 2 diabetes (T2D) and bile acids (BAs), as well as the risk of gestational diabetes mellitus (GDM). We organized a case-control study of 230 women with GDM and 217 without GDM nested in a large prospective cohort of 22 302 Chinese women in Tianjin, China. Two weighted genetic risk scores (GRSs), namely BC-GRS and IR-GRS, were established by combining 39 and 23 single nucleotide polymorphisms known to be associated with BC dysfunction and IR, respectively. Regression and mediation analyses were performed to evaluate the relationship of GRSs with BAs and GDM. We found that the BC-GRS was inversely associated with taurodeoxycholic acid (TDCA) after adjustment for confounders (Beta (SE)=-0.177 (0.048); p=2.66×10-4). The BC-GRS was also associated with the risk of GDM (OR (95% CI): 1.40 (1.10 to 1.77); p=0.005), but not mediated by TDCA. Compared with individuals in the low tertile of BC-GRS, the OR for GDM was 2.25 (95% CI 1.26 to 4.01) in the high tertile. An interaction effect of IR-GRS with taurochenodeoxycholic acid (TCDCA) on the risk of GDM was evidenced (p=0.005). Women with high IR-GRS and low concentration of TCDCA had a markedly higher OR of 14.39 (95% CI 1.59 to 130.16; p=0.018), compared with those with low IR-GRS and high TCDCA. Genetic variants related to BC dysfunction and IR in T2D potentially influence BAs at early pregnancy and the development of GDM. The identification of both modifiable and non-modifiable risk factors may facilitate the identification of high-risk individuals to prevent GDM. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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