title: Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans.
abstract: OBJECTIVE
  MTNR1B is a type 2 diabetes susceptibility locus associated with cross-sectional measures of insulin secretion. We hypothesised that variation in MTNR1B contributes to the absolute level of a diabetes-related trait, temporal rate of change in that trait, or both.
  
  
  METHODS
  We tested rs10830963 for association with cross-sectional diabetes-related traits in up to 1,383 individuals or with rate of change in the same phenotypes over a 3-5 year follow-up in up to 374 individuals from the family-based BetaGene study of Mexican Americans.
  
  
  RESULTS
  rs10830963 was associated cross-sectionally with fasting glucose (p = 0.0069), acute insulin response (AIR; p = 0.0013), disposition index (p = 0.00078), glucose effectiveness (p = 0.018) and gestational diabetes mellitus (OR 1.48; p = 0.012), but not with OGTT 30 min Δinsulin (the difference between the 30 min and fasting plasma insulin concentration) or 30 min insulin-based disposition index. rs10830963 was also associated with rate of change in fasting glucose (p = 0.043), OGTT 30 min Δinsulin (p = 0.01) and AIR (p = 0.037). There was no evidence for an association with the rate of change in beta cell compensation for insulin resistance.
  
  
  CONCLUSIONS
  We conclude that variation in MTNR1B contributes to the absolute level of insulin secretion but not to differences in the temporal rate of change in insulin secretion. The observed association with the rate of change in insulin secretion reflects the natural physiological response to changes in underlying insulin sensitivity and is not a direct effect of the variant.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of USC, 2250 Alcazar St, Los Angeles, CA, 90089-9073, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Anny H
authors.initials: AH
authors.lastname: Xiang
authors.forename: Enrique
authors.initials: E
authors.lastname: Trigo
authors.forename: Miwa
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Beale
authors.forename: Jean M
authors.initials: JM
authors.lastname: Lawrence
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Richey
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; C573871:MTNR1B protein, human; D044123:Receptor, Melatonin, MT2
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