Interleukin 1 beta (IL1ß) rs16944 genetic variant as a genetic marker of severe renal manifestations and renal sequelae in Henoch-Schönlein purpura

Data from a small series suggested that the Interleukin 1 beta (IL1ß) rs16944 polymorphism may be associated with severe renal involvement and persistent renal damage (renal sequelae) in Henoch-Schönlein purpura (HSP). To confirm this association, we assessed the largest cohort of Caucasian HSP patients ever considered for genetic studies.338 Spanish HSP patients and 635 sex and ethnically matched controls were recruited in this study. All patients were required to have had at least 6 months' follow-up. Patients and controls were genotyped for IL1β rs16944 by TaqMan genotyping assay.No differences between IL1β rs16944 genotype or allele frequencies were found either in the case/control study or when HSP patients were stratified according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Nevertheless, 4 (25%) of the 16 HSP patients who developed severe renal manifestations carried the TT genotype versus 29 (9%) of 322 who did not develop this complication (p=0.01, OR=5.48, 95% CI: 1.01-28.10). Accordingly, patients carrying the mutant T allele had an increased risk of developing severe nephropathy (p=0.016, OR=2.35, 95% CI: 1.09-5.07). Additionally, a significant increase of the TT genotype was observed in patients with persistent renal damage when compared with those patients without this complication (25% versus 8.6%, respectively; p=0.0035, OR=4.90, 95% CI: 1.26- 18.51). Moreover, renal sequelae were more common in patients carrying the mutant T allele (p=0.0076, OR=2.20, 95% CI: 1.17-4.14).Our results support that the IL1ß rs16944 polymorphism may be a potential marker of severe renal manifestations and renal sequelae in HSP.