title: Genetic variants and the risk of gestational diabetes mellitus: a systematic review.
abstract: BACKGROUND
  Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.
  
  
  METHODS
  Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.
  
  
  RESULTS
  Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P < 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P = 0.002) per T allele of rs12255372.
  
  
  CONCLUSIONS
  In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
authors.affiliation: Epidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Blvd, Rockville, MD 20852, USA.
authors.forename: Cuilin
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
authors.forename: Ying
authors.initials: Y
authors.lastname: Rong
authors.forename: Huixia
authors.initials: H
authors.lastname: Yang
authors.forename: Katherine
authors.initials: K
authors.lastname: Bowers
authors.forename: Edwina
authors.initials: E
authors.lastname: Yeung
authors.forename: Michele
authors.initials: M
authors.lastname: Kiely
mesh_terms: D000483:Alleles; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D000078790:Insulin Secretion; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics; D044122:Receptor, Melatonin, MT1 / Q000235:genetics; D044123:Receptor, Melatonin, MT2; D012306:Risk; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: C498779:IGF2BP2 protein, human; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C573871:MTNR1B protein, human; D016601:RNA-Binding Proteins; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D058118:Transcription Factor 7-Like 2 Protein; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human
keywords: gene; genetic factors; gestational diabetes mellitus; single nucleotide polymorphism