Abstract
AimsThe 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.MethodsA 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.ResultsThe 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.ConclusionsThe 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.
Highlights
The prevalence of gestational diabetes mellitus (GDM) has been rapidly increasing worldwide [1]
Using an age-matched case-control study nested in a large population-based cohort of pregnant women in Tianjin, China, this analysis aimed to explore 1) additive interactions between CDKAL1 rs7747752 polymorphism and low glycoursodeoxycholic acid (GUDCA)/deoxycholic acid (DCA) for the risk of GDM; and 2) whether the additive interactive effect if any between rs7747752 polymorphism and low GUDCA/DCA on the risk of GDM was mediated via LPC18:0 and/or SFA16:0
In order to shed light on the potential mechanisms of the additive interactions between CDKAL1 rs7747752 C allele and low GUDCA/DCA on the risk of GDM, we further conducted mediation analyses to examine whether high LPC18:0 and/or SFA16:0 can account for the association between copresence of CDKAL1 rs7747752 C allele carrier status and low GUDCA/DCA, and the increased risk of GDM
Summary
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
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