Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus.

We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (IL1RN2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of IL1RN2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of IL1RN2 and diabetic nephropathy (P<0.001, Pcorrected<0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that IL1RN2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.