Association of Common Genetic Risk Variants With Gestational Diabetes Mellitus and Their Role in GDM Prediction.

Autor:	Popova PV; Almazov National Medical Research Centre, Saint Petersburg, Russia.; Department of Internal Diseases and Endocrinology, St. Petersburg Pavlov State Medical University, Saint Petersburg, Russia., Klyushina AA; Almazov National Medical Research Centre, Saint Petersburg, Russia., Vasilyeva LB; Almazov National Medical Research Centre, Saint Petersburg, Russia., Tkachuk AS; Almazov National Medical Research Centre, Saint Petersburg, Russia., Vasukova EA; Almazov National Medical Research Centre, Saint Petersburg, Russia., Anopova AD; Almazov National Medical Research Centre, Saint Petersburg, Russia., Pustozerov EA; Almazov National Medical Research Centre, Saint Petersburg, Russia.; Department of Biomedical Engineering, Saint Petersburg State Electrotechnical University, Saint Petersburg, Russia., Gorelova IV; Almazov National Medical Research Centre, Saint Petersburg, Russia., Kravchuk EN; Almazov National Medical Research Centre, Saint Petersburg, Russia., Li O; Almazov National Medical Research Centre, Saint Petersburg, Russia., Pervunina TM; Almazov National Medical Research Centre, Saint Petersburg, Russia., Kostareva AA; Almazov National Medical Research Centre, Saint Petersburg, Russia., Grineva EN; Almazov National Medical Research Centre, Saint Petersburg, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2021 Apr 19; Vol. 12, pp. 628582. Date of Electronic Publication: 2021 Apr 19 (Print Publication: 2021).
DOI:	10.3389/fendo.2021.628582
Abstrakt:	Objective: We aimed to explore the associations between common genetic risk variants with gestational diabetes mellitus (GDM) risk in Russian women and to assess their utility in the identification of GDM cases. Methods: We conducted a case-control study including 1,142 pregnant women (688 GDM cases and 454 controls) enrolled at Almazov National Medical Research Centre. The International Association of Diabetes and Pregnancy Study Groups criteria were used to diagnose GDM. A total of 11 single- nucleotide polymorphisms (SNPs), including those in HKDC1 (rs10762264), GCK (rs1799884), MTNR1B (rs10830963 and rs1387153), TCF7L2 (rs7903146 and rs12255372), KCNJ11 (rs5219), IGF2BP2 (rs4402960), IRS1 (rs1801278), FTO (rs9939609), and CDKAL1 (rs7754840) were genotyped using Taqman assays. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). A simple-count genetic risk score (GRS) was calculated using 6 SNPs. The area under the receiver operating characteristic curve (c-statistic) was calculated for the logistic regression model predicting the risk of GDM using clinical covariates, SNPs that had shown a significant association with GDM in our study, GRS, and their combinations. Results: Two variants in MTNR1B (rs1387153 and rs10830963) demonstrated a significant association with an increased risk of GDM. The association remained significant after adjustment for age, pre-gestational BMI, arterial hypertension, GDM in history, impaired glucose tolerance, polycystic ovary syndrome, family history of diabetes, and parity (P = 0.001 and P < 0.001, respectively). After being conditioned by each other, the effect of rs1387153 on GDM predisposition weakened while the effect of rs10830963 remained significant (P = 0.004). The risk of GDM was predicted by clinical variables (c-statistic 0.712, 95 % CI: 0.675 - 0.749), and the accuracy of prediction was modestly improved by adding GRS to the model (0.719, 95 % CI 0.682 - 0.755), and more by adding only rs10830963 (0.729, 95 % CI 0.693 - 0.764). Conclusion: Among 11 SNPs associated with T2D and/or GDM in other populations, we confirmed significant association with GDM for two variants in MTNR1B in Russian women. However, these variants showed limited value in the identification of GDM cases. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Popova, Klyushina, Vasilyeva, Tkachuk, Vasukova, Anopova, Pustozerov, Gorelova, Kravchuk, Li, Pervunina, Kostareva and Grineva.)
Databáze:	MEDLINE
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