Large-Scale Candidate Gene Study of Leprosy Susceptibility in the Karonga District of Northern Malawi

Abstract

We present a large case-control candidate gene study of leprosy susceptibility. Thirty-eight polymorphic sites from 13 genes were investigated for their role in susceptibility to leprosy by comparing 270 cases with 452 controls in Karonga district, northern Malawi. Homozygotes for a silent T-->C change in codon 352 of the vitamin D receptor gene appeared to be at high risk (odds ratio [OR] = 4.3, 95% confidence interval [CI] = 1.6-11.4, P = 0.004), while homozygotes for the McCoy b blood group defining variant K1590E in exon 29 of the complement receptor 1 (formerly CD35) gene appeared to be protected (OR = 0.3, 95% CI = 0.1-0.8, P = 0.02). Borderline evidence for association with leprosy susceptibility was found for seven polymorphic sites in an additional six genes. Some of these apparent associations may be false-positive results from multiple comparisons, and several associations suggested by studies in other populations were not replicated here. These data provide evidence of inter-population heterogeneity in leprosy susceptibility.

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.…”

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

“…15 Finally, in a study among a Malawi population, proximal IL10 SNPs were not associated with leprosy. 16 In this study, we replicated the data of the IL10 promoter SNPs using a case-control design in a countryside Brazilian population from the state of São Paulo. We analyzed pooled published data using meta-analysis to clear ambiguity among papers published using À819C/T and, finally, this SNP was also a marker for in vitro genetic influence of IL-10 production.…”

“…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.…”

Genetic Polymorphisms of Infectious Diseases in Case-Control Studies

“…Thus it was a sound possibility to test TNF in a casecontrol study in leprosy, which was done in the first genetic epidemiological population-based study in leprosy that tested the −308 SNP in the promoter region of the TNF gene [17]. The association study of the region was later replicated in other studies, although they yield conflicting results [18][19][20] whose implications will be discussed later.…”