HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low viral load in cART naïve HIV-infected adult Zimbabweans. 2018

Kudakwashe Mhandire, and Mqondisi Tshabalala, and Lynn Sodai Zijenah, and Tommy Mlambo, and Doreen Zvipo Mhandire, and Cuthbert Musarurwa, and Kerina Duri, and Hilda Tendisa Matarira, and Collet Dandara, and Sarah L Rowland-Jones, and Babill Stray-Pedersen
University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. mhandiremhandire@gmail.com.

Polymorphisms in killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) gene families are implicated in differential outcomes of HIV infection. However, research findings on the influence of KIR and HLA-C polymorphism on HIV disease progression remain inconclusive. We thus investigated the association of KIR and HLA-C gene polymorphisms with plasma HIV load (VL) and CD4+ T lymphocyte (CD4) count in 183 chronically HIV-infected, combination antiretroviral therapy (cART) naïve Zimbabweans of Bantu origin. The presence or absence of 15 KIR genes were determined using sequence specific primer polymerase chain reaction while HLA-C typing was performed using chain termination DNA sequencing. Plasma VL was determined using the Cavidi Exavir viral load version 3 assay while CD4+ T lymphocytes were enumerated using flow cytometry. VLs and CD4 counts were compared between gene/genotype carriers and non-carriers using Mann-Whitney ranksum test. HLA-C*18:01 allele carriers had a significantly lower median log10 VL (2.87copies/mL [IQR;2.3-3.2]) than the non-C*18:01 carriers (3.33copies/mL [IQR; 2.74-3.9]), p = 0.018. Further, median log10 VL was significantly lower in KIR2DL2+C1 carriers (2.745 [IQR; 2.590-2.745]) than non-KIR2DL2+C1 carriers (3.4 [IQR; 2.746-3.412]), p = 0.041. Comparison of CD4 + T lymphocyte counts between C*08:02 allele carriers and non-C*08:02 carriers showed a significantly higher median CD4 count in C*08:02 carriers (548cells/µL [IQR;410-684]) than in non-carriers (428cells/µL [IQR;388-537]), p = 0.034. We conclude that the HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low VL while the C*08:02 is associated with high CD4+ T lymphocyte count among cART naïve Zimbabwean adults with chronic HIV infection.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D003430 Cross-Sectional Studies Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time. Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D015030 Zimbabwe A republic in southern Africa, east of ZAMBIA and BOTSWANA and west of MOZAMBIQUE. Its capital is Harare. It was formerly called Rhodesia and Southern Rhodesia. Rhodesia, Southern,Southern Rhodesia,Republic of Zimbabwe,Zimbabwe Rhodesia
D015236 HLA-C Antigens Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma). Antigens, HLA-C,HLA-C,Antigens, HLA C,HLA C Antigens
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D054343 Receptors, KIR2DL2 A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL1 RECEPTORS and the KIR2DL3 RECEPTORS. Antigens, CD158b1,CD158b1 Antigens,CD158b1 Antigen,KIR2DL2 Receptor,Killer Cell Immunoglobulin-like Receptor 2DL2,Natural Killer-Associated Transcript 6,Antigen, CD158b1,KIR2DL2 Receptors,Killer Cell Immunoglobulin like Receptor 2DL2,Natural Killer Associated Transcript 6,Receptor, KIR2DL2

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