title: Association 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.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.|1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
authors.forename: Klara
authors.initials: K
authors.lastname: Rosta
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Al-Aissa
authors.affiliation: 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Hadarits
authors.affiliation: Gender Medicine Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Harreiter
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Nádasdi
authors.affiliation: University of Szeged, Faculty of Medicine, Szeged, Hungary.
authors.forename: Fanni
authors.initials: F
authors.lastname: Kelemen
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bancher-Todesca
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Komlósi
authors.affiliation: Department of Probability Theory and Statistics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Németh
authors.affiliation: 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Rigó
authors.affiliation: Department of Obstetrics and Gynecology, Szent Imre Teaching Hospital, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Sziller
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Somogyi
authors.affiliation: Gender Medicine Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.|Hungarian Academy of Sciences - Semmelweis University, Molecular Medicine Research Group, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Firneisz
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C573871:MTNR1B protein, human; D044123:Receptor, Melatonin, MT2; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8