IL-10 promoter single nucleotide polymorphisms are significantly associated with resistance to leprosy

Abstract

The minor haplotype -3575A/-2849G/-2763C in IL-10 promoter has been defined as a marker of disease resistance to leprosy and its severity in Brazilian population. Our investigation of six single-nucleotide polymorphisms (SNPs) in IL-10 promoter in 282 Indian leprosy patients and 266 healthy controls by direct PCR sequencing, however, showed that the extended haplotype: -3575T/-2849G/-2763C/-1082A/-819C/-592C was associated with resistance to leprosy per se and to the development of severe form of leprosy, using either a binomial (controls vs cases, P=0.01, OR=0.58, CI=0.37-0.89) or ordinal (controls vs paucibacillary vs multibacillary, P=0.004) model. Whereas, IL-10 haplotype -3575T/-2849G/-2763C/-1082A/-819T/-592A was associated with the risk of development of severe form of leprosy (P=0.0002) in contrast to the minor risk haplotype -3575T/-2849A/-2763C in the Brazilian population. The role of IL-10 promoter SNPs in Brazilian and Indian population strongly suggests the involvement of IL-10 locus in the outcome of leprosy.

IL-10 gene promoter polymorphisms and leprosy in a Colombian population sample

“…In an Indian population the same haplotype that we found in current study, the -1082A/-819C/-592C haplotype confers resistance to leprosy and the haplotype -1082A/-819T/-592A confers susceptibility (16), whereas in a Brazilian population from Rio de Janeiro the above mentioned haplotypes were not associated with leprosy (17).…”

“…However studies carried out in different populations show variable and non-consistent results (7,13,16,17,28).…”

“…Interleukin (IL)-10 gene polymorphisms have been analyzed in several populations demonstrating the association with leprosy (15)(16)(17), however results of previous works from different populations are variable (15)(16)(17)(18)(19)(20).…”

“…For example, in an Indian population the -1082A/-819C/-592C haplotype confers resistance to leprosy and the haplotype -1082A/-819T/-592A confers susceptibility (16), whereas in a Brazilian population from Rio de Janeiro the above mentioned haplotypes were not associated with leprosy (17), but the -819T allele was associated with leprosy susceptibility per se (18). Another study from Brazil with IL-10 extended haplotypes showed that the combination of 3575A/-2849G/-2763C/-1082G/-819C was associated with resistance, and -3575T/-2849A/-2763C/-1082G/-819T was the susceptible haplotype, confirming the participation of -819T as a susceptibility allele (19 country, for example the study carried out in the Paraná State of Brazil, where the analysis of IL10 genotypes did not show any significant differences between leprosy patients and controls (7).…”

HLA-DRB1*04 and DRB1*10 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients

“…9,[24][25][26][27] have been implicated in leprosy susceptibility, corroborated by result replication in more than one population. Thus, it is likely that genetic heterogeneity is a common feature of this disease, but other genes are also involved, as expected in any complex trait.…”