Body mass index associated to rs2021966 ENPP1 polymorphism increases the risk for gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) is a condition of impaired glucose tolerance occurring in 1-14% of all pregnancies. This wide range reflects pathological involvement of single nucleotide polymorphisms (SNPs) and maternal weight as risk factors. This study evaluated the association of genetic component and maternal factors to identify women with higher risk of developing GDM. About 240 pregnant women characterized by negative Oral Glucose Tolerance Test (-OGTT) and 38 with positive OGGT (+OGTT) were enrolled. SNPs for ENPP1, NRF1, VEGFA, CEBPA, and PIK3R1 were analyzed by SNP genotyping. An association study was performed and differences in genotype and allele frequencies between cases and controls were analyzed by χ(2) test. +OGTT was associated to high values of pre-gestational body mass index (BMI) and age. SNP for ENPP1 gene was associated to +OGTT, while genetic variants for other genes did not correlate to GDM. ENPP1 homozygous for A allele and heterozygous showed altered frequencies in +OGTT when compared with -OGTT. Association of both pre-gestational BMI and age with AA homozygous genotype increased significantly the risk to +OGTT. Our results demonstrate that correlation of age and pre-gestational BMI with homozygous for A allele increased significantly the risk of impaired glucose tolerance and GDM.

Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: a Global Perspective

“…In particular, although Asians generally have a lower body mass index (BMI), they are more prone to accumulate visceral fat and develop abdominal obesity at a given BMI [44], which in turn are positively associated with insulin resistance and impaired β cell function [45, 46]. Genetic predisposition may also contribute to the excessively high prevalence of GDM among certain high-risk racial/ethnic groups [47, 48]. Moreover, the risk of GDM may vary by nativity even within the same racial/ethnic group.…”

Gestational diabetes: An overview with attention for developing countries

“…Reactive oxygen species have an important role in pathogenesis of almost all chronic metabolic diseases and in GDM they lead insulin resistance. GDM -gestational diabetes mellitus; BMI -body mass index; TNF-α -tumor necrosis factor-α; IL-6 -interleukin-6; AFABPadipocyte fatty acid-binding protein; EPC -endothelial progenitor cells gestational high body weight and body mass index (BMI) increased signifi cantly the risk of impaired glucose tolerance and GDM (Tarquini et al 2015).…”

An observational study of the risk of neonatal macrosomia, and early gestational diabetes associated with selected candidate genes for type 2 diabetes mellitus polymorphisms in women with gestational diabetes mellitus

“…Also, data from GDM cohorts refer to only a few T2DM candidate genes out of a large number of identified risk variants. Additionaly, for some associations, maternal BMI was found to be a possible or actual determining factor explaining the relationships found by researchers [7][8][9][10].…”