The common T60N polymorphism of the lymphotoxin-alpha gene is associated with type 2 diabetes and other phenotypes of the metabolic syndrome.
OBJECTIVE
Associations between variations in the lymphotoxin-alpha 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
The T60N LTA polymorphism is associated with type 2 diabetes and other features of the metabolic syndrome among Caucasian individuals.
Hamid
Y H
YH
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark. yah@steno.dk
Urhammer
S A
SA
Glümer
C
C
Borch-Johnsen
K
K
Jørgensen
T
T
Hansen
T
T
Pedersen
O
O
D000328:Adult; D017668:Age of Onset; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People
D001786:Blood Glucose; D007328:Insulin; D008233:Lymphotoxin-alpha
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