The +3187A/G HLA-G polymorphic site is associated with polar forms and reactive reaction in leprosy

Abstract

Considering that variability in immune response genes has been associated withsusceptibility to leprosy and with disease severity, leprosy presents clinicopathologicalvariants that are highly associated with the immune response, HLA-Ghas a well-recognized role in the modulation of the immune response, andpolymorphisms at the 3′ untranslated region (UTR) of the HLA-G gene mayinfluence HLA-G production, we studied the polymorphic sites at the 3′ UTRof the HLA-G gene in leprosy and their association with disease severity. Weevaluated by sequencing analysis the allele, genotype, and haplotype frequenciesof the 3′ UTR HLA-G polymorphic sites (14-bpINDEL/+3003C-T/+3010CG/+3027A-C/+3035C-T/+3142C-G/+3187A-G/+3196C-G) in 146 individualspresenting reactive leprosy from a highly endemic area, and associated withbacillary load and the type of reactive leprosy. A total of 128 healthy subjectswere also studied. Allele, genotype, and haplotype frequencies for the 3′ UTRHLA-G polymorphisms in leprosy patients did not differ from those observedin healthy donors. The +3187A allele was responsible for protection against thedevelopment of multibacillary leprosy in a dominant model (AA + AG)/GG,OR = 0.11, P = 0.018), and the +3187A allele and +3187A-A genotype wereoverrepresented in type II reactive leprosy reaction. The effect of genetic factorson leprosy susceptibility may be hidden by environmental components inhighly endemic areas. The HLA-G + 3187A polymorphic site, which is relatedto unstable mRNA production, was associated with the development of polarforms of leprosy and reactive leprosy reaction.