Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy

We have determined IL-10 promoter genotypes of five single-nucleotide polymorphisms (SNPs): T−3575A, A−2849G, C−2763A, -A−1082G and C−819T. The haplotype frequencies were defined in healthy subjects compared to leprosy patients, and analyzed for their occurrence in multi- (MB) vs paucibacillary (PB) as severe and mild forms of leprosy, respectively. Haplotypes defined by three SNP positions (−3575, −2849 and −2763) captured significant differences between controls and patients (P=0.04). The haplotype carrying −3575A, −2849G and −2763C was associated with resistance to leprosy and to the development of severe forms of the disease using either a binomial (controls vs cases, P=0.005, OR=0.35, CI=0.13–0.91) or ordinal (controls vs PB vs MB, P=0.006, OR=0.32, CI=0.12–0.83) model. By contrast, the IL-10 haplotype −3575T/−2849A/−2763C was found to be associated with susceptibility to leprosy per se (P=0.027, OR=2.37, CI=1.04–5.39), but not leprosy type. The data suggest that the IL-10 locus contributes to the outcome of leprosy.