title: CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea.
abstract: Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G >A, CCR5 -2459G >A and Δ32, and CXCL12 801G >A in PNG (n=258), North America (n=184), and five countries in West Africa (n=178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 -2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 -2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-values<0.001). Regardless of whether we considered the CXCL12 801 AA genotype protective or susceptible, the risk scores were significantly higher in the PNG population compared with any other population (all P-values<0.001). The results of this study provide new insights regarding CCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Mehlotra
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Noemi B
authors.initials: NB
authors.lastname: Hall
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Bruse
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Bangan
authors.initials: B
authors.lastname: John
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Melinda J Blood
authors.initials: MJB
authors.lastname: Zikursh
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.|Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
mesh_terms: D044383:Black People / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D010219:Papua New Guinea; D011401:Promoter Regions, Genetic / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D018570:Risk Assessment
chemical_list: C515334:CCR2 protein, human; C584933:CCR5 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D054390:Receptors, CCR2; D019713:Receptors, CCR5
keywords: CCR2; CCR5; CXCL12; HIV; Papua New Guinea