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

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

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.808956

DOI=10.3389/fendo.2022.808956

ISSN=1664-2392

ABSTRACT=<sec><title>Aims</title><p>The study aimed to explore additive interactions of <italic>CDKAL1</italic> rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated <italic>via</italic> increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>The <italic>CDKAL1</italic> rs7747752 was associated with GDM (P&lt;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.</p></sec><sec><title>Conclusions</title><p>The <italic>CDKAL1</italic> 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 <italic>via</italic> increasing LPC18:0.</p></sec>