Acta Tropica 140 (2014) 130–136 Contents lists available at ScienceDirect Acta Tropica jo u r n al homep age: www.elsevier.com/locate/actatropica SLC11A1 polymorphisms and susceptibility to visceral leishmaniasis in Moroccan patients Rajaâ Ejghal a,b , Moustapha Hida c , Mona Lakhdar Idrissi c , Aboubaker El Hessni b , Meryem Lemrani a,∗ a Laboratoire de parasitologie et maladies vectorielles, Institut Pasteur du Maroc, Casablanca, Morocco b Laboratory of Genetic, Neuroendocrinology and Biotechnology, Faculty of Science, University Ibn Tofaïl, B.P 133, 14 000 Kénitra, Morocco c Faculty of Medicine and Pharmacy, University Sidi Mohammed ben abdellah, route de Sefrou, Fes, Morocco a r t i c l e i n f o Article history: Received 4 June 2014 Received in revised form 8 August 2014 Accepted 11 August 2014 Available online 20 August 2014 Keywords: Visceral leishmaniasis Leishmania infantum Asymptomatic infection Host susceptibility SLC11A1 polymorphisms Moroccan children a b s t r a c t Human visceral leishmaniasis is endemic in the Mediterranean basin. Since most infections are sub- clinical 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 intra- cellular 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 leish- maniasis 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 leishman- iasis 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. © 2014 Published by Elsevier B.V. 1. Introduction Leishmaniasis currently threatens 350 million people in 98 countries around the world (WHO, 2010). Visceral leishmaniasis (VL), also known as kala-azar, is the most severe form of the dis- ease and is often fatal if left untreated. Epidemiological status of VL is described in 61 countries in four continents, where about 200 million people are at risk. The worldwide incidence of VL is approx- imately 0.5 million cases per year (Desjeux, 2004), and although incidence is contracting, the disease remain a major and serious public health problem in many countries. In Morocco, VL is caused by L. infantum, predominantly affecting children under the age of 9 years (Ministry of Health, 2008). The incidence of VL is estimated at ∗ Corresponding author. Tel.: +212 661 46 48 18; fax: +212 522 26 09 57. E-mail address: meryem.lemrani@pasteur.ma (M. Lemrani). 150 cases per year (Ministry of Health, 2008) however, the disease is spreading at a fast pace in the northern rural regions of the country. Leishmania parasites possess a variety of virulence mechanisms that enable the amastigote stage to survive in the hostile environ- ment of the phagolysosome (Blackwell, 1996). Infection with this protozoan can result in asymptomatic infection, or disseminated disease with hepatosplenomegaly, fever, cachexia, and immuno- compromised (Searle et al., 1998). In endemic areas, asymptomatic infection is common and is associated with the development of delayed type hypersensitivity (DTH) response to Leishmania (Marty et al., 1992). The immune response against Leishmania can be sub- stantially modified by factors such as host nutritional status, age, and genetic background (Desjeux, 2004; Mohamed et al., 2004). A better understanding of the genetic risk factors that determine host susceptibility could provide important leads for improved therapies (Blackwell et al., 2009). Characterizing the genes and pro- teins implicated in natural resistance may identify key host mech- anisms of defense and novel targets for therapeutic intervention in http://dx.doi.org/10.1016/j.actatropica.2014.08.013 0001-706X/© 2014 Published by Elsevier B.V.