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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

A paired-sibling analysis of the XbaI polymorphism in the muscle glycogen synthase gene

Author

  • Marju Orho-Melander
  • Peter Almgren
  • T Kanninen
  • C Forsblom
  • Leif Groop

Summary, in English

AIMS/HYPOTHESIS: We have previously shown an association between a XbaI polymorphism in the muscle glycogen synthase gene (GYS1) and both Type II (non-insulin-dependent) diabetes mellitus and hypertension. Association studies are, however, hampered by the selection of the control group. To circumvent these problems we addressed the same question using a novel genotype discordant paired-sibling approach. METHODS: We identified 122 sex-matched sib-pairs discordant for the Xba1 polymorphism among a new set of 743 Finnish subjects from 227 families with Type II diabetes and paired analyses were done by McNemar test of symmetry and by permutation tests. RESULTS: Paired analysis showed that siblings with the A2 variant had more hypertension (p = 0.0067), obesity (p = 0.033) and microalbuminuria (p = 0.031) but not significantly more Type II diabetes (p = 0.27) than siblings with the A1 variant. Siblings with the A2 variant were more often treated by insulin (p = 0.050) or anti-hypertensive medication (p = 0.0060) or both. Diabetic A2 variant carriers had higher triglyceride (p = 0.023) and lower HDL cholesterol (p = 0.0059) concentrations and an earlier age at onset of diabetes (p = 0.022) than diabetic siblings with the A1 variant. In non-diabetic sib-pairs the presence of the A2 variant was associated with higher diastolic (p = 0.0014) blood pressure. Finally, the allele frequency of the XbaI polymorphism differed between 216 randomly chosen unrelated Type II diabetic patients and 115 unrelated healthy control spouses without a family history of Type II diabetes (12.7 vs. 6.5 %, p = 0.013). CONCLUSION/INTERPRETATION: The A2 allele of the XbaI polymorphism in the GYS1 confers an increased susceptibility to different features of the metabolic syndrome and Type II diabetes.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

1999

Language

English

Pages

1138-1145

Publication/Series

Diabetologia

Volume

42

Issue

9

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Muscle glycogen synthase gene
  • GYS1
  • paired-sibling analysis
  • Type II diabetes
  • hypertension
  • metabolic syndrome
  • chromosome 19
  • candidate gene
  • myocardial infarction
  • microalbuminuria

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1432-0428