Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release.
OBJECTIVE
The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals.


METHODS
We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middle-aged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes.


RESULTS
There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middle-aged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels.


CONCLUSIONS
The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.
Hansen
S K
SK
Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, 2820 Gentofte, Denmark. sakf@steno.dk
Gjesing
A P
AP
Rasmussen
S K
SK
Glümer
C
C
Urhammer
S A
SA
Andersen
G
G
Rose
C S
CS
Drivsholm
T
T
Torekov
S K
SK
Jensen
D P
DP
Ekstrøm
C T
CT
Borch-Johnsen
K
K
Jørgensen
T
T
McCarthy
M I
MI
Hansen
T
T
Pedersen
O
O
D000328:Adult; D000483:Alleles; D001724:Birth Weight / Q000502:physiology; D001786:Blood Glucose / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D003718:Denmark / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005838:Genotype; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D016695:Glycosyltransferases