背景:遗传之间的相互作用,新陈代谢,环境因素导致妊娠期糖尿病(GDM)。我们旨在研究低血清水平L-肉碱的细胞周期蛋白依赖性激酶5调节亚基相关蛋白1样1(CDKAL1)rs7747752多态性的相互作用。胆碱,和甜菜碱用于GDM。
方法:对207名GDM妇女及其一对一的巢式病例对照研究,年龄匹配的对照组来自天津孕妇的前瞻性队列,中国。使用条件逻辑回归检验CDKAL1rs7747752与L-肉碱血清水平之间的关联,胆碱,和甜菜碱,以及GDM的风险。进行了加性相互作用,以检查rs7747752和低血清水平的L-肉碱的相互作用效应,胆碱,和甜菜碱对GDM的风险。
结果:CDKAL1rs7747752G>C在添加剂中与GDM相关,支配,和隐性模型(P<0.05)。rs7747752CC基因型增强L-肉碱≤vs.从6.14(2.61-14.4)到19.6(5.65-68.1)的GDM>150nmol/mL,胆碱的OR≤vs.从2.37(1.07-5.28)到12.1(3.22-45.6)>110nmol/mL,具有显著的加性相互作用。同样,CG基因型也提高了L-肉碱≤vs.>150nmol/mL的GDM从4.70(2.01-11.0)到11.4(3.98-32.9),具有显著的加性相互作用。然而,rs7747752和甜菜碱≤200nmol/mL对GDM风险的累加作用不显著.
结论:CDKAL1rs7747752中具有低血清L-肉碱或胆碱水平的CC或CG基因型携带者具有特别高的GDM风险。有必要进行随机对照试验,以测试补充L-肉碱或胆碱对高危人群GDM风险的影响。
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.