The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

Hui Wang; Jing Li; Junhong Leng; Weiqin Li; Jinnan Liu; Xiaoyan Yan; Zhijie Yu; Gang Hu; Ronald C W Ma; Zhongze Fang; Ying Wang; Xilin Yang

doi:10.3389/fendo.2022.808956

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

Front Endocrinol (Lausanne). 2022 Mar 10:13:808956. doi: 10.3389/fendo.2022.808956. eCollection 2022.

Authors

Hui Wang¹, Jing Li^{1

2

3}, Junhong Leng⁴, Weiqin Li⁴, Jinnan Liu¹, Xiaoyan Yan⁵, Zhijie Yu⁶, Gang Hu⁷, Ronald C W Ma⁸, Zhongze Fang^{2

3

9}, Ying Wang¹⁰, Xilin Yang^{1

2

3}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
² Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China.
³ Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China.
⁴ Project Office, Tianjin Women and Children's Health Center, Tianjin, China.
⁵ School of Public Health, Shanxi Medical University, Shanxi, China.
⁶ Population Cancer Research Program and Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
⁷ Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States.
⁸ Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁹ Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China.
¹⁰ Scientific Research Platform of the Second School of Clinical Medicine & Key Laboratory of 3D Printing Technology in Stomatology, Guangdong Medical University, Dongguan, China.

Abstract

Aims: The study aimed to explore additive interactions of CDKAL1 rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated via increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0.

Methods: A 1:1 age-matched study nested in a prospective cohort of pregnant women (207 pairs) was organized in Tianjin, China. Additive interactions were used to test interaction effects while mediation analyses and Sobel tests were used to test mediation effects of LPC18:0 and SFA16:0 between copresence of rs7747752 and low GUDCA/DCA, and GDM risk.

Results: The CDKAL1 rs7747752 was associated with GDM (P<0.05). The rs7747752 C polymorphism markedly enhanced ORs of low GUDCA from 4.04 (0.72-22.8) to 9.02 (1.63-49.7) and low DCA from 1.67 (0.68-4.11) to 4.24 (1.84-9.76), both with significant additive interactions. Further adjustment for LPC18:0 attenuated the interactive effects of rs7747752 and low DCA, with a significant mediation effect (P=0.003). High SFA16:0 did not mediate the interactive effects of rs7747752 and low DCA/GUDCA on GDM risk.

Conclusions: The CDKAL1 rs7747752 C carrier status and low GUDCA/DCA had significant additive interactions on the risk of GDM with the effect from interaction with DCA being partially mediated via increasing LPC18:0.

Keywords: CDKAL1; deoxycholic acid; gestational diabetes mellitus; glycoursodeoxycholic acid; rs7747752.

MeSH terms

Bile Acids and Salts
Case-Control Studies
Diabetes, Gestational* / epidemiology
Diabetes, Gestational* / genetics
Female
Humans
Pregnancy
Prospective Studies
Risk Factors
tRNA Methyltransferases* / genetics

Substances

Bile Acids and Salts
tRNA Methyltransferases
CDKAL1 protein, human