title: Common variants of HNF1A gene are associated with diabetic retinopathy and poor glycemic control in normal-weight Japanese subjects with type 2 diabetes mellitus.
abstract: OBJECTIVE
  This study investigated the associations between the common hepatocyte nuclear factor-1A (HNF1A) variants and the risk of diabetic retinopathy (DR) in relation to the glycemic control and weight status.
  
  
  METHODS
  A retrospective longitudinal analysis was conducted among 354 Japanese patients with type 2 diabetes mellitus (T2DM) (mean follow-up duration: 5.8±2.5 years). The multivariable-adjusted hazard ratio (HR) for the cumulative incidence of DR was calculated using a Cox proportional hazard model. During the observation period, the longitudinal associations of the HNF1A diplotypes with the risk of DR and the clinical parameters were also analyzed using the generalized estimating equations approach.
  
  
  RESULTS
  The combination of risk variants, i.e., rs1169288-C, rs1183910-A and rs2464196-A, was defined as the H1 haplotype. The incidence of DR was higher in the H1/H1 diplotype cases than in the others (HR 2.75 vs. non-H1/non-H1; p=0.02). Only in normal-weight subjects, the risks of DR and poor glycemic control were higher in the H1/H1 diplotype cases than in the others [odds ratio 4.08 vs. non-H1/non-H1, p=0.02; odds ratio 3.03, p=0.01; respectively].
  
  
  CONCLUSIONS
  This study demonstrated that the common HNF1A diplotype of three risk variants may be an independent risk factor for the development of DR resulting from poor glycemic control in normal-weight patients with T2DM. These results need to be replicated in larger and more varied study populations.
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Kajiwara
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Jinnouchi Clinic, Diabetes Care Center, Kumamoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Jinnouchi Clinic, Diabetes Care Center, Kumamoto, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: kazukon@gpo.kumamoto-u.ac.jp.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D015992:Body Mass Index; D003131:Combined Modality Therapy / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000208:ethnology / Q000628:therapy; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000032:analysis; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000517:prevention & control*; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications / Q000208:ethnology; D015995:Prevalence; D012189:Retrospective Studies
chemical_list: D006442:Glycated Hemoglobin; D051538:Hepatocyte Nuclear Factor 1-alpha; C496487:HNF1A protein, human; C517652:hemoglobin A1c protein, human
keywords: Diabetic retinopathy; Hemoglobin A1c; Hepatocyte nuclear factor-1A; Longitudinal study; Normal-weight