Genetic determinants for gestational diabetes mellitus and related metabolic traits in Mexican women

PLoS One. 2015 May 14;10(5):e0126408. doi: 10.1371/journal.pone.0126408. eCollection 2015.

Abstract

Epidemiological and physiological similarities among Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes (T2D) suggest that both diseases, share a common genetic background. T2D risk variants have been associated to GDM susceptibility. However, the genetic architecture of GDM is not yet completely understood. We analyzed 176 SNPs for 115 loci previously associated to T2D, GDM and body mass index (BMI), as well as a set of 118 Ancestry Informative Markers (AIMs), in 750 pregnant Mexican women. Association with GDM was found for two of the most frequently replicated T2D loci: a TCF7L2 haplotype (CTTC: rs7901695, rs4506565, rs7903146, rs12243326; P=2.16 x 10(-06); OR=2.95) and a KCNQ1 haplotype (TTT: rs2237892, rs163184, rs2237897; P=1.98 x 10(-05); OR=0.55). In addition, we found two loci associated to glycemic traits: CENTD2 (60' OGTT glycemia: rs1552224, P=0.03727) and MTNR1B (HOMA B: rs1387153, P=0.05358). Remarkably, a major susceptibility SLC16A11 locus for T2D in Mexicans was not shown to play a role in GDM risk. The fact that two of the main T2D associated loci also contribute to the risk of developing GDM in Mexicans, confirm that both diseases share a common genetic background. However, lack of association with a Native American contribution T2D risk haplotype, SLC16A11, suggests that other genetic mechanisms may be in play for GDM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / genetics
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / epidemiology
  • Diabetes, Gestational / genetics*
  • Female
  • GTPase-Activating Proteins / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • Mexico / epidemiology
  • Monocarboxylic Acid Transporters / genetics
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Receptor, Melatonin, MT2 / genetics
  • Transcription Factor 7-Like 2 Protein / genetics
  • Young Adult

Substances

  • ARAP1 protein, human
  • Carrier Proteins
  • GTPase-Activating Proteins
  • KCNQ1 Potassium Channel
  • MTNR1B protein, human
  • Monocarboxylic Acid Transporters
  • Receptor, Melatonin, MT2
  • SLC16A11 protein, human
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein

Associated data

  • Dryad/10.5061/dryad.KQ0K2
  • dbGaP/PHS000683.V1.P1

Grants and funding

This project was supported by the Fondo Sectorial de Investigación en Salud, grant number: 115250. AHC and PVC received support through graduate fellowships provided by the Consejo Nacional de Ciencia y Tecnología (CONACyT) (http://www.conacyt.mx). The SIGMA T2D Diabetes Project was conducted as part of the Slim Initiative for Genomic Medicine, a joint US-Mexico project funded by the Carlos Slim Health Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.