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

Abstract

We have determined IL-10 promoter genotypes of five single-nucleotide polymorphisms (SNPs): TÀ3575A, AÀ2849G, CÀ2763A, -AÀ1082G and CÀ819T. 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 (À3575, À2849 and À2763) captured significant differences between controls and patients (P ¼ 0.04). The haplotype carrying À3575A, À2849G and À2763C was associated with resistance to leprosy and to the development of severe forms of the disease using either a binomial (controls vs cases, P ¼ 0.005, OR ¼ 0.35, CI ¼ 0.13-0.91) or ordinal (controls vs PB vs MB, P ¼ 0.006, OR ¼ 0.32, CI ¼ 0.12-0.83) model. By contrast, the IL-10 haplotype À3575T/ À2849A/À2763C was found to be associated with susceptibility to leprosy per se (P ¼ 0.027, OR ¼ 2.37, CI ¼ 1.04-5.39), but not leprosy type. The data suggest that the IL-10 locus contributes to the outcome of leprosy.

Genetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for −819C/T in leprosy susceptibility

“…This result was reinforced with meta-analysis, in which the SNP À819C/T was tested in association with leprosy. [13][14][15][16] The pooled sample reached a total of 2702 individuals (1355 cases and 1347 controls), including subjects belonging to three Brazilian, one Malawian and one Indian populations (total of five populations). We pooled data from papers found in the literature using key words, but also included our data that were not selected in a canonical way to compare with all selected papers for meta-analysis, but the results with or without our case-control study show basically the same: association of À819T with leprosy susceptibility.…”

“…Santos et al 13 showed that À819T allele was associated with leprosy susceptibility. Later, extended haplotypes were studied and the combination of À3575A/À2849G/À2763C/ À1082G/À819C was associated with resistance, whereas À3575T/À2849A/À2763C/À1082G/À819T was the susceptible haplotype 14 confirming the participation of À819T as a susceptibility allele of the locus. A replication study carried out in Indians implicated a different promoter haplotype associated with leprosy susceptibility (À3575T/À2849G/À2763C/À1082A/À819T/À592A), but again À819T was associated with the disease outcome.…”

“…PCR amplifications were carried out as described 14 with modifications. Briefly, PCR mix was carried out with 50 ng of genomic DNA, 10 pmol of each specific primer, 0.5 U of Taq DNA polymerase (Invitrogen, São Paulo, SP, Brazil), 0.2 mM of each dNTP (Invitrogen, Carlsbad, CA, USA) and 1.5 mM of MgCl 2 in a final reaction volume of 12.5 ml using a thermal cycler (MJ Research PTC100, Hercules, CA, USA).…”

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

“…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).…”

“…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).…”