Abstract
BackgroundThe outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population.MethodsAn existing DNA repository of 200 each of patients and controls was typed for HLA-DQ by PCR-SSP. Next generation sequencing-based typing for HLA-A, HLA-B and HLA-DRB1 alleles was done in a subset of 280 samples. Association tests were performed on 28,489 genotyped and imputed SNPs spanning a region of 1.4 Mb across the HLA genes. To compare our results with similar studies, we carried out a systematic review to document all HLA associations reported to-date for cutaneous and muco-cutaneous leishmaniasis.ResultsDRB1*04 DQB1*02 (P = 0.03; Pc = 0.09), DRB1*07 DQB1*02 (P = 0.03; Pc = 0.09) haplotypes were absent in patients. B*07 (P = 0.007; Pc = 0.13; OR = 0.36; 95 % CI = 0.17–0.77) allele and DRB1*15 DQB1*06 (P = 0.00; Pc < 0.01; OR = 0.3; 95 % CI = 0.2–.0.6) haplotype were over represented in controls and DRB1*15 (P = 0.002; Pc = 0.01) allele was over represented in patients. Two SNPs (rs281864595/rs1050517) in the antigen recognition region of HLA-B, comprised a haplotype more frequent in controls (P = 0.04). The alleles identified by the systematic review to predispose or to protect from cutaneous/mucocutaneous leishmaniasis remained highly heterogeneous in different populations studied.ConclusionsOur preliminary findings suggest a role for some class I and class II HLA genes in determining predisposition to LCL in this population which should be corroborated with further studies. The systematic review reiterates this need, as the purported susceptibility or protection gained by certain HLA alleles or haplotypes has rarely been independently verified.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1626-8) contains supplementary material, which is available to authorized users.
Highlights
The outcome of leishmaniasis is an interplay between Leishamania and the host
The present study investigated a potential association between localized cutaneous leishmaniasis (LCL) and class I and II human leucocyte antigen (HLA) loci in a South Asian population by comparing the distribution of HLAA, HLA-B, HLA-DRB1 and HLA-DQB1 alleles in patients and healthy controls
B*07 followed by B*40 were the two most common HLA-B alleles in both patients and controls out of 10 alleles which were common to both groups
Summary
Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population. Caused by a protozoan parasite of the genus Leishmania and transmitted by the sandfly, this is a disease with a spectrum of phenotypes ranging from self-healing localized skin lesions to potentially fatal visceral disease. The severity of cutaneous disease depends on both the extent of parasite replication and the relative induction of immunopathologic responses by the host. The genetic background is considered the single most important host factor which modulates these immune responses [3,4,5,6]
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