Effect of gene-lifestyle interaction on gestational diabetes risk

Abstract

We hypothesized that the association of certain lifestyle parameters with gestational diabetes mellitus (GDM) risk would depend on susceptibility loci. In total, 278 Russian women with GDM and 179 controls completed questionnaires about lifestyle habits (food consumption, physical activity and smoking). GDM was diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Maternal blood was sampled for genotyping single-nucleotide polymorphisms (SNPs) in MTNR1B (rs10830963 and rs1387153), GCK (rs1799884), KCNJ11 (rs5219), IGF2BP2 (rs4402960), TCF7L2 (rs7903146 and rs12255372), CDKAL1 (rs7754840), IRS1 (rs1801278) and FTO (rs9939609). Binary logistic regression revealed an interaction effect of sausage intake and the number of risk alleles of two SNPs (rs10830963 in MTNR1B and rs1799884 in GCK) on GDM risk (P < 0.001). Among women without risk alleles of these two SNPs, sausage consumption was positively associated with GDM risk (P trend = 0.045). This difference was not revealed in women carrying 1 or more risk alleles. The risk of GDM increased as the number of risk alles increased in participants with low and moderate sausage consumption (P trend <0.001 and 0.006, respectively), while the risk of GDM in women with high sausage consumption remained relatively high, independent of the number of risk alleles. These findings indicate that the association of sausage consumption with GDM risk can be determined based on the number of risk alleles of rs10830963 in MTNR1B and rs1799884 in GCK.

Molecular Biomarkers for Gestational Diabetes Mellitus

“…Of the five studies investigating rs12255372, two showed an association between the T allele and GDM, one was conducted in a large Swedish population and the other in a small Mexican population [ 42 , 43 ]. However, these results were not replicated in studies conducted in Russian, Spanish, or Brazilian populations [ 39 , 41 , 47 ] of moderate size, suggesting that ethnic or other confounding factors underlie these differences. The T allele is associated with decreased insulin production and altered hepatic gluconeogenesis [ 48 ], and therefore, is a good candidate for further research in larger cohorts, despite these conflicting results obtained in these studies.…”

“…Genetic studies of the transcription factor 7 like 2 ( TCF7L2 ) gene, which is arguably one of the most important T2D susceptibility genes [ 36 ], produced varying results in GDM [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. TCF7L2 encodes a transcription factor, which is involved in Wnt signaling, an important pathway that regulates glucose homeostasis.…”

Identification and Potential Clinical Utility of the MTNR1B rs10830963 Core Gene Variant Associated to Endophenotypes in Gestational Diabetes Mellitus

“…In contrast, independent case-control genetic studies report OR values between 1.29 and 2. for GDM development in Middle European (Vejrazkova et al, 2014;Rosta et al, 2017), Mediterranean Hispanic (García de la Torre et al, 2019), Middle Eastern (Alharbi et al, 2019) Asian (Wu et al, 2016) and Russian (Popova et al, 2017) pregnant populations. The MTNR1B rs10830963 associated effects appeared to be more preponderant provided that the mean pre-pregnancy BMI was above 25 kg/m 2 (Wu et al, 2016).…”

“…Furthermore, it was independently reported (Grotenfelt et al, 2016) that the rs10830963 G risk allele carrying significantly decreased the odds with a similar effect size (OR for intervention failure in G allele carriers >5) of responding to an early (from the 13th gestational week) medical nutrition therapy and lifestyle intervention in high-risk (pre-pregnancy BMI ≥ 30 kg/m 2 and/or prior GDM) Finnish pregnant women. In addition the MTNR1B rs10830963 variant is reported to augment the effect of lifestyle risk factors and dietary habits (in particular sausage consumption) on GDM development (Popova et al, 2017).…”

The Role of Glycemic Index and Glycemic Load in the Development of Real-Time Postprandial Glycemic Response Prediction Models for Patients with Gestational Diabetes

“…All parameters were assessed separately before and during pregnancy. This questionnaire has been previously reported [25,26].…”