Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data

Abstract

Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and allcause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n=350), Gargano Mortality Study (n=698) and Foggia Mortality Study (n=431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p=3.5*10−7) with effect size modest for GRS=1 and 2 and much higher for GRS >3, with respect to GRS=0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p=3.3*10−2), with a low effect size for GRS=1 and 2, and nearly doubled for GRS≥3, with respect to GRS=0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22–3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients.