The diabetic epidemic is increasing worldwide. The suppressor of cytokine signaling 3 (SOCS3) provides a link between cytokine action and their negative consequences on insulin signaling. This potential influence on the development of T2DM makes the gene a potential candidate gene for type 2 diabetes.
We investigated the one haplotype tagging single nucleotide polymorphism (htSNP) rs4969168 to examine the impact on T2DM in two independent study populations; one prospective case-cohort study and one cross-sectional cohort. In the prospective cohort a total of 2,242 individuals (669 had developed T2DM during the follow-up period) were analyzed. In the dominant model there was no effect of the polymorphism on diabetes risk (hazard ratio (95% CI): 0.86 (0.661.13); P=0.3). In the second, cross-sectional MeSyBePo-cohort 1,897 subjects (325 had T2DM) were investigated. Accordingly to the prospective results, no association with T2DM was found (odds ratio (95% CI): 0.78 (0.541.12); P=0.8). We also calculated the power in our cohorts, to estimate the detectable effect. This resulted for the EPIC-cohort in a relative risk under 0.72 or above 1.35 and for the MeSyBePo-cohort under 0.66 and above 1.44.
In conclusion there is no strong effect of the one htSNP in the SOCS3 gene on the development of T2DM. However, the impact of genetic variants on complex diseases is usually quite small. Thus a small effect might still exist, which has not been detected by our cohorts, although a total of more than 4000 individuals was investigated.