A paired-sibling analysis of the XbaI polymorphism in the muscle glycogen synthase gene
Författare
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.
Avdelning/ar
Publiceringsår
1999
Språk
Engelska
Sidor
1138-1145
Publikation/Tidskrift/Serie
Diabetologia
Volym
42
Issue
9
Dokumenttyp
Artikel i tidskrift
Förlag
Springer
Ämne
- Endocrinology and Diabetes
Nyckelord
- Muscle glycogen synthase gene
- GYS1
- paired-sibling analysis
- Type II diabetes
- hypertension
- metabolic syndrome
- chromosome 19
- candidate gene
- myocardial infarction
- microalbuminuria
Status
Published
Forskningsgrupp
- Genomics, Diabetes and Endocrinology
ISBN/ISSN/Övrigt
- ISSN: 1432-0428