title: Associations between the common HNF1A gene variant p.I27L (rs1169288) and risk of type 2 diabetes mellitus are influenced by weight.
abstract: OBJECTIVE
  The common variants p.I27L (rs1169288), p.A98V (rs1800574) and p.S487N (rs2464196) of the hepatocyte nuclear factor 1-α (HNF1A) gene have been inconsistently associated with impaired glucose tolerance and/or an increased risk of type 2 diabetes mellitus (T2DM). The present study aimed to investigate whether these associations are affected by weight.
  
  
  METHODS
  A cross-sectional analysis was conducted among 861 Japanese subjects (males: 65.5%; 61.8±12.3years) attending a health-screening programme. Interactive effects between HNF1A variants and weight status on risk of T2DM or dysglycaemic status were determined.
  
  
  RESULTS
  The 27L variant carriers were at higher risk of T2DM and dysglycaemic status than non-carriers, but only in normal-weight subjects [odds ratio (OR): 2.04, P=0.03 and OR: 2.56, P=0.01, respectively]. An interactive effect of the p.I27L (rs1169288) variant and weight status on the risk of dysglycaemic status was found (P=0.04). Age, but not body mass index (BMI), was a risk factor for dysglycaemic status in the 27L carriers (OR: 1.05, P=0.0003), whereas BMI was a risk factor in non-carriers (OR: 1.23, P=0.008). No carriers of 98V were identified, and 487N was not associated with either T2DM or dysglycaemic status in our study population.
  
  
  CONCLUSIONS
  These findings suggest that the HNF1A p.I27L (rs1169288) variant may be a significant risk factor of T2DM in normal-weight subjects and that earlier inconsistent results may have been due, in part, to subjects' weight status. Further investigations in larger cohorts are needed to verify these findings.
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, 862-0973 Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Morita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, 862-0973 Kumamoto, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Saruwatari
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, 862-0973 Kumamoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, 862-0973 Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oniki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, 862-0973 Kumamoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kajiwara
authors.affiliation: Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Otake
authors.affiliation: Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, 862-0973 Kumamoto, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: kazukon@gpo.kumamoto-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D001835:Body Weight / Q000502:physiology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha
keywords: Glucose intolerance; Hepatocyte nuclear factor 1-α; Overweight; Type 2 diabetes