title: KIR Gene Content Diversity in a Zimbabwean Population: Does KIR2DL2 Have a Role in Protection Against Human Immunodeficiency Virus Infection?
abstract: Killer cell immunoglobulin-like receptors (KIRs) mediate natural killer cell function through interaction with their cognate human leukocyte antigen ligands. Thus, KIR gene variants have been implicated in resistance or susceptibility to viral infections. However, research on the role of these variants remains contradictory and inconclusive. In the present study, we investigated KIR gene content diversity and its association with human immunodeficiency virus (HIV) infection in an adult Black Zimbabwean population. Presence or absence of 15 KIR genes was determined in 189 HIV-infected adults and 97 HIV-uninfected blood donors using sequence specific primer polymerase chain reaction. Frequencies of KIR genes, genotypes, and haplotypes were compared between the cases and controls to identify putative associations between KIR gene variants and HIV status. We report in this study the frequencies of 15 KIR genes and 43 KIR genotypes (40 known and 3 novel) among Zimbabweans. Importantly, the frequency of the inhibitory KIR2DL2 gene was significantly higher in the uninfected group (62%) compared to the HIV-infected group (47%) (OR = 0.55, 95% CI: 0.33-0.90, p = 0.019). KIR2DL2/2DL2 homozygosity was also significantly higher in the uninfected group (35%) compared to HIV-infected group (53%) (OR = 0.33, 95% CI: 0.16-0.72, p = 0.005) under a recessive model. We conclude that the KIR2DL2 gene may be involved in protection against HIV infection. It may be possible that inhibitory KIR genes may have an important role to play in HIV acquisition among populations of African origin in whom the activating KIR genes are less frequent compared to among Caucasians.
authors.affiliation: 1 Department of Chemical Pathology, College of Health Sciences, University of Zimbabwe , Harare, Zimbabwe .|2 Letten Foundation Research House , Harare, Zimbabwe .
authors.forename: Kudakwashe
authors.initials: K
authors.lastname: Mhandire
authors.affiliation: 3 Department of Immunology, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Lynn Sodai
authors.initials: LS
authors.lastname: Zijenah
authors.affiliation: 4 Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom .
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Yindom
authors.affiliation: 3 Department of Immunology, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Kerina
authors.initials: K
authors.lastname: Duri
authors.affiliation: 3 Department of Immunology, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Tommy
authors.initials: T
authors.lastname: Mlambo
authors.affiliation: 3 Department of Immunology, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Mqondisi
authors.initials: M
authors.lastname: Tshabalala
authors.affiliation: 3 Department of Immunology, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Lovemore Ronald
authors.initials: LR
authors.lastname: Mazengera
authors.affiliation: 1 Department of Chemical Pathology, College of Health Sciences, University of Zimbabwe , Harare, Zimbabwe .|2 Letten Foundation Research House , Harare, Zimbabwe .
authors.forename: Doreen Zvipo
authors.initials: DZ
authors.lastname: Mhandire
authors.affiliation: 1 Department of Chemical Pathology, College of Health Sciences, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Cuthbert
authors.initials: C
authors.lastname: Musarurwa
authors.affiliation: 5 Division of Human Genetics, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.affiliation: 4 Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom .
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.affiliation: 1 Department of Chemical Pathology, College of Health Sciences, University of Zimbabwe , Harare, Zimbabwe .
authors.forename: Hilda Tendisa
authors.initials: HT
authors.lastname: Matarira
authors.affiliation: 2 Letten Foundation Research House , Harare, Zimbabwe .|6 Institute of Clinical Medicine, University of Oslo and Womens' Clinic, Rikshospitalet, University Hospital , Oslo, Norway .
authors.forename: Babill
authors.initials: B
authors.lastname: Stray-Pedersen
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D054340:Receptors, KIR / Q000235:genetics; D015030:Zimbabwe
chemical_list: D054340:Receptors, KIR
keywords: Black Zimbabweans; HIV infection; HLA; Inhibitory KIR; gene content variation