title: SLC11A1 polymorphisms and host susceptibility to cutaneous leishmaniasis in Pakistan.
abstract: The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan.
  
  
  
  Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r2= 64); and rs17235409 and rs17235416 (r2= 78).
  
  
  
  This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan.
authors.affiliation: Karachi Institute of Biotechnology & Genetic Engineering (KIBGE), University of Karachi, Karachi, 75270, Pakistan. mariamsophie@gmail.com.
authors.forename: Mariam
authors.initials: M
authors.lastname: Sophie
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), 24-Mauve Area, G- 9/1, Islamabad, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
authors.affiliation: Kuwait Teaching Hospital, Abdara Chowk, University Road, Peshawar, Pakistan.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Muneer
authors.affiliation: National Medical Centre, A-5/A, National Highway, Phase 1, Defence Housing Authority, Karachi, Pakistan.
authors.forename: Azam J
authors.initials: AJ
authors.lastname: Samdani
authors.affiliation: Karachi Institute of Biotechnology & Genetic Engineering (KIBGE), University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Saleem
authors.affiliation: Karachi Institute of Biotechnology & Genetic Engineering (KIBGE), University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Abid
authors.initials: A
authors.lastname: Azhar
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology* / Q000235:genetics*; D010154:Pakistan / Q000453:epidemiology; D011110:Polymorphism, Genetic; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1
keywords: Cutaneous leishmaniasis; Genetic susceptibility; Pakistan; SLC11A1; Single nucleotide polymorphism