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Open Access 01-12-2016 | Research article

Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review

Authors: Nilakshi Samaranayake, Sumadhya D. Fernando, Nilaksha F. Neththikumara, Chaturaka Rodrigo, Nadira D. Karunaweera, Vajira H. W. Dissanayake

Published in: BMC Infectious Diseases | Issue 1/2016

Abstract

Background

The 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.

Methods

An 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.

Results

DRB1*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.

Conclusions

Our 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.

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Samaranayake N, Fernando SD, Rodrigo C, Neththikumara N, Karunaweera N, Dissanayake V. Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review. BMC Infect Dis. 2016. In Press.

Title: Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review
Authors: Nilakshi Samaranayake
Sumadhya D. Fernando
Nilaksha F. Neththikumara
Chaturaka Rodrigo
Nadira D. Karunaweera
Vajira H. W. Dissanayake
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-016-1626-8

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Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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