IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly post-diagnosis.
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.
ID- alleles are only clearly distinguished from all other alleles by an MSPI(-) variant within IGF2 downstream of the minisatellite, suggesting that the apparent role of the minisatellite in susceptibility to T1DM may be modified by neighbouring haplotype and therefore that IDDM2 could have a multi-locus aetiology.
Furthermore, the (+) allele of an ApaI polymorphism in the 3'-untranslated region of IGF2 was associated with significantly higher IGF2 messenger ribonucleic acid levels than the (-) allele, but was not associated with type 1 diabetes.
We evaluated this hypothesis by comparing IGF2 expression levels from chromosomes with the protective class III alleles to those with class I alleles in tissues relevant to type 1 diabetes pathogenesis.
IDDM2-encoded predisposition to type 1 diabetes has recently been mapped to the minisatellite or variable number of tandem repeat (VNTR) locus upstream of the insulin and insulin-like growth factor II genes on human chromosome 11p15.5.
Although association of insulin-dependent diabetes mellitus with a haplotype at a locus encompassing the genes for insulin and the insulin-like growth factor II has been well established, two major studies disagree as to whether linkage to this locus is confined to paternally inherited alleles, or is present in alleles transmitted from either parental sex.