%0 Journal Article %T Interactions of CDKAL1 rs7747752 polymorphism and serum levels of L-carnitine and choline are related to increased risk of gestational diabetes mellitus. %A Wang H %A Li J %A Liu J %A Leng J %A Li W %A Yu Z %A Tam CHT %A Hu G %A Ma RCW %A Fang Z %A Wang Y %A Yang X %J Genes Nutr %V 17 %N 1 %D Oct 2022 1 %M 36183068 %F 4.423 %R 10.1186/s12263-022-00716-9 %X BACKGROUND: Interactions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1(CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM.
METHODS: A nested case-control study of 207 GDM women and their one-to-one, age-matched controls was organized from a prospective cohort of pregnant women in Tianjin, China. Conditional logistic regressions were used to test associations between CDKAL1 rs7747752 and serum levels of L-carnitine, choline, and betaine, and the risk of GDM. Additive interactions were performed to examine interactive effects of rs7747752 and low serum levels of L-carnitine, choline, and betaine on the risk of GDM.
RESULTS: The CDKAL1 rs7747752 G > C was associated with GDM in additive, dominant, and recessive model (P <0.05). The rs7747752 CC genotype enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 6.14 (2.61-14.4) to 19.6 (5.65-68.1) and the OR of choline ≤ vs. > 110 nmol/mL from 2.37 (1.07-5.28) to 12.1 (3.22-45.6), with significant additive interactions. Similarly, CG genotype also enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 4.70 (2.01-11.0) to 11.4 (3.98-32.9), with a significant additive interaction. However, the additive interaction between rs7747752 and betaine ≤ 200 nmol/mL on the risk of GDM was not significant.
CONCLUSIONS: The CC or CG genotype carriers in rs7747752 of CDKAL1 who have a low serum level of L-carnitine or choline are at a particular high risk of GDM. Randomized controlled trials are warranted to test the effect of supplement of L-carnitine or choline on the risk of GDM in the high-risk group.