Published in:
01-03-2005 | Article
The common T60N polymorphism of the lymphotoxin-α gene is associated with type 2 diabetes and other phenotypes of the metabolic syndrome
Authors:
Y. H. Hamid, S. A. Urhammer, C. Glümer, K. Borch-Johnsen, T. Jørgensen, T. Hansen, O. Pedersen
Published in:
Diabetologia
|
Issue 3/2005
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Abstract
Aims/hypothesis
Associations between variations in the lymphotoxin-α gene (LTA) and myocardial infarction, cerebral infarction and type 1 diabetes have previously been reported. We hypothesised that, in its homozygous form, the functional T60N variant of LTA is associated with type 2 diabetes and other features of the metabolic syndrome among Danish Caucasian individuals.
Methods
The T60N polymorphism of LTA was genotyped in the population-based Inter99 study cohort (6,514 Caucasian subjects) and in a group of type 2 diabetic patients by analysis of PCR-generated primer extension products using high-throughput chip-based matrix-assisted laser desorption/ionisation time-of-flight mass spectronomy.
Results
Comparison of 1,401 diabetic patients with 1,470 matched glucose-tolerant control subjects from the Inter99 cohort revealed that the frequency of the mutant at codon 60 in its homozygous form (N/N genotype) was higher among the diabetic patients than among the control subjects (14.6% [95% CI 12.8–16.5] vs 12.0% [95% CI 10.3–13.7], p=0.048; odds ratio=1.24). This association was even stronger among the 131 patients with early-onset (diagnosis at 40 years or younger) diabetes (21.4% [95% CI 14.4–28.4] vs 12.0% [95% CI 10.3–13.7], p=0.004; odds ratio=1.99). Additionally, studies of the metabolic syndrome (as defined by the 1999 World Health Organization criteria) in the Inter99 study cohort revealed that the frequency of the N/N LTA genotype was higher among subjects presenting one or more features of the metabolic syndrome (n=4,425) than among subjects with no characteristics of this syndrome (n=1,752) (p=0.026).
Conclusions/interpretation
The T60N LTA polymorphism is associated with type 2 diabetes and other features of the metabolic syndrome among Caucasian individuals.