Evidence for a Type 1 diabetes-specific mechanism for the insulin gene-associated IDDM2 locus rather than a general influence on autoimmunity.
OBJECTIVE
The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5' upstream of the insulin (INS) and insulin-like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self-tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes-specific locus or acting as a general autoimmunity gene.


METHODS
We genotyped the INS-IGF2 VNTR [using the surrogate INS-23 HphI single nucleotide polymorphism (SNP)] in 823 Graves' disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects.


RESULTS
We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case-control dataset showed no genotypic or allelic difference between the two populations.


CONCLUSIONS
These data suggest that the INS-IGF2 VNTR is acting as a Type 1 diabetes-specific susceptibility gene rather than as an influence on general autoimmunity.
Tait
K F
KF
Division of Medical Sciences, University of Birmingham, UK.
Collins
J E
JE
Heward
J M
JM
Eaves
I
I
Snook
H
H
Franklyn
J A
JA
Barnett
A H
AH
Todd
J A
JA
Maranian
M
M
Compston
A
A
Sawcer
S
S
Gough
S C L
SC
D000483:Alleles; D001327:Autoimmune Diseases / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006111:Graves Disease / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D007328:Insulin; D007335:Insulin-Like Growth Factor II