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

Alicia Huerta-Chagoya,Hortensia Moreno-Macías,Rosario Rodríguez-Guillén,Rogelio Zacarías-Castillo,Carlos Aguilar-Salinas,Lizette Manzo-Carrillo,Erika López-Vite,Leonardo Tapia-Maruri,Fernando Escobedo-Aguirre,Guadalupe García-Escalante,Teresa Tusié-Luna,Carlos Vargas-García,Roberto Cordero-Brieño,Paola Vázquez-Cárdenas,Adalberto Parra-Covarrubias,Florian Kronenberg

doi:10.1371/journal.pone.0126408

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=2.16x10-06; OR=2.95) and a KCNQ1 haplotype (TTT: rs2237892, rs163184, rs2237897; P=1.98x10-05; 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.

Highlights

Gestational Diabetes Mellitus (GDM) is defined as a condition of carbohydrate intolerance of varying severity that begins or is first recognized during pregnancy and is a common obstetric complication
Did we find TCF7L2 and KCNQ1 variants to be associated to GDM, but GDM cases reported higher frequency of family history of diabetes than controls
In the recent SIGMA Type 2 Diabetes (T2D) GWAS in Mexicans, it was demonstrated that common variants within the TCF7L2 and KCNQ1 genes were among the strongest associated loci [14]

Summary

Introduction

Gestational Diabetes Mellitus (GDM) is defined as a condition of carbohydrate intolerance of varying severity that begins or is first recognized during pregnancy and is a common obstetric complication. It is characterized by an impaired compensatory increase in insulin secretion to overcome the pregnancy-induced insulin resistance. It has been reported that common T2D risk genetic variants confer predisposition to GDM development in Caucasian and Asian populations [4, 5], but up to date, there is scarce information in other ethnic groups. Common T2D risk genetic variants associated to GDM risk include: TCF7L2 (rs7903146), MTNR1B (rs10830962, rs10830963), IGF2BP2 (rs4402960, rs1470579), KCNJ11 (rs5219), CDKAL1 (rs7754840, rs7756992), KCNQ1 (rs2237892, rs2237895), GCK (rs4607517), CDKN2A/2B (rs2383208, rs10811661), SRR (rs391300), HHEX (rs1111875, rs5015480, rs7923837), SLC30A8 (rs13266634), TCF2 (rs7501939)

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