Open AccessAssociation Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development
Author(s) -
Klára Rosta,
Zahra Al-Aissa,
Orsolya Hadarits,
Jürgen Harreiter,
Ákos Nádasdi,
Fanni Kelemen,
Dagmar BancherTodesca,
Zsolt István Komlósi,
László Németh,
János Rigó,
István Sziller,
Anikó Somogyi,
Alexandra KautzkyWiller,
Gábor Firneisz
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0169781
Subject(s) - gestational diabetes , single nucleotide polymorphism , odds ratio , tcf7l2 , medicine , genotyping , case control study , minor allele frequency , biology , genetics , genotype , pregnancy , gestation , gene
Context Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). Objective We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. Methods 960 pregnant women (after dropouts 820: case/control: m99’WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m’99WHO criteria based on standard OGTT values. Results The most important risk alleles associated with GDM were rs10830963/ G of MTNR1B (OR = 1.84/1.64 [IADPSG/m’99WHO], p = 0.0007/0.006), rs7754840/ C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/ T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/ T ( SLC30A8 , OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/ G ( LOC646736/IRS1 , OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 ( MTNR1B ); rs7903146 ( TCF7L2 ); rs1799884 ( GCK ) SNPs were associated with increased plasma glucose levels at routine OGTT. Conclusions We confirmed the robust association of MTNR1B rs10830963/ G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/ T SNP ( SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99’WHO and the IADPSG GDM diagnostic criteria.