SLC11A1 polymorphisms and susceptibility to visceral leishmaniasis in Moroccan patients

Human visceral leishmaniasis is endemic in the Mediterranean basin. Since most infections are subclinical or asymptomatic, host genetics can provide concrete evidence in determining disease outcome. SLC11A1/NRAMP1 is a candidate gene that may be related to host susceptibility versus resistance to intracellular pathogens. This study aimed to determine possible association of SLC11A1 polymorphisms with visceral leishmaniasis among Moroccan children. A total of 106 children who developed visceral leishmaniasis due to Leishmania infantum were enrolled in this study. The control group was composed of 137 unrelated children, 97 asymptomatic subjects (DTH+) and 42 healthy individuals (DTH) who had no evidence of present or past infection. Four polymorphisms were studied by PCR-RFLP and sequencing: (GT)n microsatellite in the 5' exon 1; silent substitutions 469 + 14G/C in intron 4; amino acid substitution D543N in exon 15 and 823C/T polymorphism in exon 8. Thereafter, the frequencies of genotypes, alleles and haplotypes were estimated. Two polymorphisms were each significantly associated in the genotypes with visceral leishmaniasis: 823C/T in exon 8 and D543N in exon 15 when comparing visceral leishmaniasis and DTH+ groups. The results of haplotype frequencies suggested an evidence of association with resistance to visceral leishmaniasis for the "286GTG" and "288GCA" haplotypes, whereas, the "286GCG" haplotype appears to increase the risk to visceral leishmaniasis susceptibility. Our data provide insights into the possible role of SLC11A1 variation in visceral leishmaniasis susceptibility. These results must be regarded as preliminary but suggestive that further study with larger populations is worthwhile. (C) 2014 Elsevier B.V. All rights reserved.