Interleukin-1 receptor antagonist gene polymorphisms are associated with disease severity in Black South Africans with rheumatoid arthritis

ObjectiveTo test for genetic associations between polymorphisms of the interleukin-1 (IL-1) gene cluster and disease susceptibility and severity in Black South Africans with rheumatoid arthritis (RA).MethodsAllele and genotype frequencies of IL1B (−511) and (+3954) and IL1RN variable number of tandem repeat (VNTR) and (+2018) were compared between 141 RA patients and 101 healthy controls.ResultsNo significant differences in allelic distribution at the four loci were observed between RA patients and controls. Within the RA group, the IL1RN*2 (two repeats of an 86 bp tandem repeat) at the IL1RN VNTR locus was independently associated with higher Larsen radiologic damage scores (LDS), corrected for disease duration (p = 0.04). Moreover, the inferred haplotype, consisting of IL1RN*2 and (+2018) ‘C’ allele, was associated with significantly higher LDS, on average 15 points higher, compared to the base haplotype of IL1RN*long (three or more repeats) and (+2018) ‘T’ allele (p = 0.009). The common IL1B (−511) ‘T’ allele was associated with a poorer modified health assessment questionnaire disability index (p = 0.02).ConclusionOur findings provide further evidence of a possible role of polymorphisms of the IL-1 gene cluster in disease severity in RA, and particularly IL1RN*2 as a marker of erosive joint damage in Black South Africans with RA.