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

Orho-Melander, Marju LU ; Almgren, Peter LU ; Kanninen, T; Forsblom, C and Groop, Leif LU (1999) In Diabetologia 42(9). p.1138-1145
Abstract
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 =... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Muscle glycogen synthase gene, GYS1, paired-sibling analysis, Type II diabetes, hypertension, metabolic syndrome, chromosome 19, candidate gene, myocardial infarction, microalbuminuria
in
Diabetologia
volume
42
issue
9
pages
1138 - 1145
publisher
Springer Verlag
external identifiers
  • pmid:10447527
  • scopus:0032868004
ISSN
1432-0428
DOI
10.1007/s001250051282
language
English
LU publication?
yes
id
3a295a91-3271-42d2-ba11-087c3b95e541 (old id 1115656)
date added to LUP
2008-07-08 11:02:32
date last changed
2017-01-01 04:59:52
@article{3a295a91-3271-42d2-ba11-087c3b95e541,
  abstract     = {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.},
  author       = {Orho-Melander, Marju and Almgren, Peter and Kanninen, T and Forsblom, C and Groop, Leif},
  issn         = {1432-0428},
  keyword      = {Muscle glycogen synthase gene,GYS1,paired-sibling analysis,Type II diabetes,hypertension,metabolic syndrome,chromosome 19,candidate gene,myocardial infarction,microalbuminuria},
  language     = {eng},
  number       = {9},
  pages        = {1138--1145},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {A paired-sibling analysis of the XbaI polymorphism in the muscle glycogen synthase gene},
  url          = {http://dx.doi.org/10.1007/s001250051282},
  volume       = {42},
  year         = {1999},
}