Aims/hypothesis
Beta cell loss in Type 1 and Type 2 diabetes mellitus may result from apoptosis and necrosis induced by inflammatory mediators. The suppressor of cytokine signalling (SOCS)-3 is a natural inhibitor of cytokine signalling and also influences insulin signalling. SOCS3 could therefore be a candidate gene in the development of Type 1 and Type 2 diabetes mellitus.Methods
Mutation analysis of the SOCS3 gene was performed in 21 patients with Type 1 diabetes mellitus and in seven healthy subjects. An identified promoter variant was examined in (i) 250 families with Type 1 diabetic family members (1097 individuals); (ii) 212 glucose-tolerant first-degree relatives of Type 2 diabetic patients; and (iii) 370 population-based young, healthy subjects who were unrelated.Results
Three mutations were identified in the promoter region, but none in the coding region or the 3
UTR. Two of the three mutations had allele frequencies below 1% whereas the C –920
A substitution had a minor allele frequency of 8%. In the group of young healthy subjects the insulin sensitivity index was higher among homozygous carriers of the
A-allele than among heterozygous and wild-type subjects (
p=0.027, uncorrected). The same trend was found in the group of first-degree relatives of Type 2 diabetic patients. No association or linkage was found to Type 1 diabetes mellitus.
Conclusions/interpretation
Homozygosity for the
A-allele of the C –920
A promoter polymorphism of the
SOCS3 gene may be associated with increased whole-body insulin sensitivity, but deserves further investigation.
Keywords Beta cell - Cytokines - Diabetes - Insulin sensitivity - Insulin signalling - Mutation scanning - Promoter