A paired-sibling analysis of the XbaI polymorphism in the muscle glycogen synthase gene
(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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https://lup.lub.lu.se/record/1115656
- author
- Orho-Melander, Marju LU ; Almgren, Peter LU ; Kanninen, T ; Forsblom, C and Groop, Leif LU
- organization
- publishing date
- 1999
- 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
- 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
- 2016-04-01 12:16:24
- date last changed
- 2024-01-08 14:35:13
@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}},
keywords = {{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}},
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}},
doi = {{10.1007/s001250051282}},
volume = {{42}},
year = {{1999}},
}