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

Objective: To 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). Methods: Allele 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. Results: No 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). Conclusion: Our 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.