Browse by author
Lookup NU author(s): Professor Mark Walker
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Variation at the variable number tandem repeat (VNTR) minisatellite 5' of the insulin gene (INS) is associated with several phenotypes, including type 1 diabetes, polycystic ovary syndrome, and birth weight. Case-control studies have suggested that class III VNTR alleles are also associated with type 2 diabetes, but results have been inconsistent and may reflect population stratification. To explore further the role of the INS-VNTR in type 2 diabetes susceptibility, we used family-based association methods in 155 parent-offspring trios from the British Diabetic Association-Warren Trios repository, each ascertained via a Europid proband with type 2 diabetes. Overall, there was no significant association between diabetes and the INS- VNTR genotype, with 65 of 119 heterozygous parents (55%) transmitting class III and 54 class I (P = 0.16, one-sided). However, whereas maternal transmissions followed Mendelian expectation, there was a marked excess of class III transmission from the 49 heterozygous fathers (34 [69%] vs. 15, P = 0.003 vs. 50% expectation, P = 0.003 vs. maternal transmission). These results confirm that variation within the TH-INS-IGF2 locus, most plausibly at the VNTR itself, influences type 2 diabetes susceptibility. By demonstrating that this effect is mediated exclusively by the paternally derived allele, these findings implicate imprinted genes in the pathogenesis of type 2 diabetes.
Author(s): Walker M; Huxtable SJ; McCarthy MI; Saker PJ; Haddad L; Frayling TM; Levy JC; Hitman GA; O'Rahilly S; Hattersley AT
Publication type: Article
Publication status: Published
Journal: Diabetes
Year: 2000
Volume: 49
Issue: 1
Pages: 126-130
ISSN (print): 0012-1797
ISSN (electronic): 1939-327X
Publisher: The American Diabetes Association
URL: http://dx.doi.org/10.2337/diabetes.49.1.126
DOI: 10.2337/diabetes.49.1.126
PubMed id: 10615960
Altmetrics provided by Altmetric
