INTERLEUKIN-1 RECEPTOR ANTAGONIST ALLELE (IL1RN(ASTERISK)2) ASSOCIATED WITH NEPHROPATHY IN DIABETES-MELLITUS

We have previously found association between an allele of the interleu kin-l (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanis m. We have now, therefore, tested the association of this specific all ele (IL1RN2) with complications of diabetes which have an inflammator y 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 betwee n carriage of IL1RN2 and diabetic nephropathy (P < 0.0001, P-correcte d < 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 marke r of disease susceptibility. If the DNA polymorphism is associated wit h altered gene function, new therapeutic interventions may be possible .