title: The Arg121Trp variant in PAX4 gene is associated with beta-cell dysfunction in Japanese subjects with type 2 diabetes mellitus.
abstract: Mutations in PAX4, a transcription factor involved in the beta-cell differentiation, could predispose to the development of type 2 diabetes mellitus. To clarify the role of PAX4 Arg121Trp mutation on the development of type 2 diabetes mellitus, we try to determine the clinical phenotype in diabetic subjects with this mutation. Study subjects consisted of 793 type 2 diabetic patients and 318 control subjects. Genotyping for Arg121Trp polymorphism was performed by Invader assay. Clinical phenotype was determined in diabetic subjects including 20 Trp121 carriers and 142 wild-type subjects using a combination of 2-compartment model of C-peptide kinetics and minimal model analysis during intravenous glucose tolerance test. We detected 3 Trp/Trp, 51 Arg/Trp, and 739 Arg/Arg in diabetic subjects, and 16 Arg/Trp and 302 Arg/Arg in control subjects. The frequency of Trp121 allele was 3.59% and 2.51% in diabetic and control groups, respectively (P = .19). Rate of insulin users was higher in Trp121 carriers compared with the wild-type group (42.5% vs 25.0%, P = .0046). First-phase C-peptide secretion was significantly decreased in the diabetic subjects with Trp121 allele compared with the patients with wild type (P = .0048), whereas there were no significant differences in insulin sensitivity and glucose effectiveness between the groups. Arg121Trp mutation in PAX4 gene could be associated with beta-cell dysfunction in Japanese subjects with type 2 diabetes mellitus.
authors.affiliation: Diabetes Center, Chiba Central Medical Center, Chiba 264-0017, Japan. yt4486yt@yahoo.co.jp
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tokuyama
authors.forename: Kana
authors.initials: K
authors.lastname: Matsui
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Toru
authors.initials: T
authors.lastname: Egashira
authors.forename: Azuma
authors.initials: A
authors.lastname: Kanatsuka
mesh_terms: D000483:Alleles; D044466:Asian People; D002097:C-Reactive Protein / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D007564:Japan; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; D002097:C-Reactive Protein; D004247:DNA