No association between insulin gene variation and adult metabolic phenotypes in a large Finnish birth cohort.
OBJECTIVE
Although the variable number tandem repeat (VNTR) minisatellite 5' to the insulin gene is among the most studied polymorphisms in diabetes, the relationships between VNTR variation, diabetes-related traits and predisposition to type 2 diabetes remain unclear. Since inadequate sample size is likely to have been an obstacle to reliable inference, we examined the relationship between VNTR variation and a range of diabetes-related traits in a cohort of 5,753 Finnish adults.


METHODS
VNTR genotypes were derived, by typing at the -23HphI variant site, for 5,646 individuals from the Northern Finland Birth Cohort 1966. Associations were sought between these genotypes and a range of anthropometric (BMI, WHR), physiological (blood pressure) and biochemical (fasting glucose, insulin, lipids, indices of insulin sensitivity and beta cell function) measures obtained at clinical examination at 31 years.


RESULTS
We found no evidence that VNTR genotype was significantly associated with measures of insulin secretion, insulin sensitivity, glycaemia, adiposity or blood pressure.


CONCLUSIONS
Despite evidence from several relatively small studies suggesting that INS-VNTR genotypes are associated with predisposition to type 2 diabetes, reduced beta cell function and measures of adiposity, the present study failed to detect any association with a range of diabetes-related traits. Taken with other recent studies in large population-based cohorts, these data suggest that previous studies have, at the very least, overestimated the influence of the INS-VNTR on type 2 diabetes-related traits. The effects of INS-VNTR variation on insulin transcription observed in vitro appear not to translate into detectable differences in basal insulin secretion in humans.
Bennett
A
A
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital Site, Old Road, Headington, Oxford OX3 7LJ, UK.
Sovio
U
U
Ruokonen
A
A
Martikainen
H
H
Pouta
A
A
Taponen
S
S
Hartikainen
A-L
AL
Franks
S
S
Peltonen
L
L
Elliott
P
P
Järvelin
M-R
MR
McCarthy
M I
MI
D000328:Adult; D001722:Birth Order; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D015331:Cohort Studies; D005387:Finland; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D000078790:Insulin Secretion; D008055:Lipids / Q000097:blood; D018598:Minisatellite Repeats
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids