Diabetologia

, Volume 39, Issue 3, pp 349–352 | Cite as

Association of Trp64Arg mutation of the β3-adrenergic-receptor with NIDDM and body weight gain

  • T. Fujisawa
  • H. Ikegami
  • E. Yamato
  • K. Takekawa
  • Y. Nakagawa
  • Y. Hamada
  • T. Oga
  • H. Ueda
  • M. Shintani
  • M. Fukuda
  • T. Ogihara
Rapid Communications

Summary

A possible pathogenic mutation in the Β3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects. Since marked heterogeneity has been reported in the association of mutations of candidate genes with NIDDM between Japanese and other ethnic groups, we investigated the association of Trp64Arg with NIDDM in Japanese subjects. The allele frequency of the mutation (Arg) was slightly, but not significantly, higher in NIDDM than in control subjects (70 out of 342 alleles [20.5%] vs 40 out of 248 [16.1%], respectively, p>0.2). When our data were combined with those of Pima Indian and Finnish subjects, however, the Arg/Arg genotype was significantly associated with NIDDM as compared with the other two genotypes (p<0.005, relative risk [RR] 2.13, 95% confidence interval [CI] 1.28–3.55). The Arg allele was also associated with NIDDM (p<0.05, RR 1.27, 95% CI 1.06–1.52). Japanese subjects homozygous for the mutation had a significantly higher body mass index (mean ± SD∶25.5±3.9 kg/ m2) than heterozygotes (22.6±4.1, p<0.05) and normal homozygotes (22.8±3.8, p<0.05). NIDDM patients homozygous for the mutation tended to have an earlier age of onset of NIDDM than those with other genotypes. These data suggest that the Trp64Arg mutation not only contributes to weight gain and age-at-onset of NIDDM but is also associated with susceptibility to NIDDM.

Keywords

Β3-adrenergic-receptor gene susceptibility missense mutation non-insulin-dependent diabetes mellitus insulin resistance syndrome 

Abbreviations

NIDDM

Non-insulin-dependent diabetes mellitus

Β3-AR

Β3-adrenergic-receptor

Trp64Arg

a mutation in the Β3-adrenergic-receptor gene causing a Trp to Arg change at codon 64

BMI

body mass index

ADRB3

Β3-adrenergic receptor gene

PCR

polymerase chain reaction

RFLP

restriction fragment length polymorphism

RR

relative risk

CI

confidence interval

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • T. Fujisawa
    • 1
  • H. Ikegami
    • 1
  • E. Yamato
    • 1
  • K. Takekawa
    • 1
  • Y. Nakagawa
    • 1
  • Y. Hamada
    • 1
  • T. Oga
    • 1
  • H. Ueda
    • 1
  • M. Shintani
    • 1
  • M. Fukuda
    • 2
  • T. Ogihara
    • 1
  1. 1.Department of Geriatric MedicineOsaka University Medical SchoolOsakaJapan
  2. 2.Department of OphthalmologyOsaka Teishin HospitalOsakaJapan

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