Abstract
Background: Cysteine-Cysteine Chemokine Receptor 5 (CCR5), also referred to as CD195, is a component of the mammalian cell membrane and is receptor for chemokines that are activated during cell damage and inflammations. This receptor is coded by a gene located in the human chromosome 3. A Mutation on this CCR5 through deletion of 32 base pairs results into a non-destructive gene CCR5Δ32. It enables protection against HIV infection to its homozygous carriers and slows progression of the disease to heterozygous carriers. Objective: To systematically review and establish global distribution of CCR5Δ32 allele in HIV-1 infected individuals over the history of the epidemic and compare regions inhabited by Caucasians, Asians and Africans. Methodology: This meta-analysis comprised of published papers with over 10,000 individuals from whom CCR5-Delta 32 allele was successfully genotyped and recorded. The study review period was from 1984 to 2017. The search targeted online sources such as Hinari specifically PubMed Central, Google scholar, Science Direct, Research4Life, National Center for Biotechnology Information (NCBI), OVID databases, AIDS Journal and Google. The searches were not limited to a particular publication language or study design but excluded letters of correspondence and conference presentations. Search strategy using key words from a combination of Medical Subject Heading (MeSH) and free text including terms related to CCR5, CCR5Δ32 and HIV were performed in Medical Literature Analysis and Retrieval System Online (MEDLINE) through Ovid Open Access. Additional studies were identified by perusing the reference list of relevant and included articles. The review considered studies conducted among general population, both HIV positive and HIV negative individuals, exposed seronegatives (ESN), exposed seropositives (ESP) and highly exposed seronegatives (HESN) and resultant data pooled using a fixed effect model. Results: A total of 40 studies comprising 10,871 participants were reviewed. These were from three main regions: Europe, Africa and Asia. Of the studies accessed and reviewed, Caucasians were 22.5%, Africans were 12.5%, Europeans were 27% and others (not specified) were 37.5%. The distribution of CCR5Δ32 allele among different populations in comparison to its heterozygosity displayed significant association with a pooled Odds Ratio (OR) of 0.08 (95% CI, 0.03 - 0.18, P < 0.00001), test of subgroup differences at I2 = 0% and a P value of 0.50. Among the Caucasians alone the OR was at 0.04 (95% CI, 0.01 - 0.19, I2 = 96%) and a significant P value of < 0.00001 displaying a high presence of CCR5Δ32 homozygosity as compared to Europeans with OR of 0.09 (95% CI, 0.04 - 0.19, I2 = 21%, P = 0.25) and Africans with OR 0.25 (95% CI, 0.03 - 2.29, I2 = 0%, P = 0.81); an indication that race can be a factor that determines CCR5Δ32 homozygosity or heterozygosity and it highly favors the Caucasians. Out of 136 homozygous carriers found in the review Europeans had 6%, Caucasian 93%, Africans 0% and others combined 0.7%. Conclusion: The distribution of CCR5Δ32, an allele that is associated with lower acquisition of HIV/AIDS is at 93% among the Caucasians. The remaining 7% is shared amongst the rest of the populations, hence high susceptibility to the disease. Minimal availability of recorded data experienced in this study is a clear indication that there exist major gaps in studies that could further associate CCR5Δ32 allele frequency and HIV infection in different populations. The review recommends a mixture of population genetics and epidemiological studies in trying to understand the increasing rates of HIV prevalence among selected groups.
Highlights
Mammalian cell membranes have cysteine-cysteine chemokine receptor 5 (CCR5) as a component
To systematically review and establish global distribution of CCR5Δ32 allele in HIV-1 infected individuals over the history of the epidemic and compare regions inhabited by Caucasians, Asians and Africans
Search strategy using key words from a combination of Medical Subject Heading (MeSH) and free text including terms related to CCR5, CCR5Δ32 and HIV were performed in Medical Literature Analysis and Retrieval System Online (MEDLINE) through Ovid Open Access
Summary
Mammalian cell membranes have cysteine-cysteine chemokine receptor 5 (CCR5) as a component They are referred to as CD195 and are popularly known for allowing in chemokines that signal cellular response during inflammation and after cellular damages [1]. The CCR5-Delta 32 (CCR5Δ32) is a damage resulting from a deletion of 32 base pairs of the CCR5 gene but the mutation is non-deleterious. Previous studies have shown that individuals having homozygosity in CCR5Δ32 are hindered from HIV acquisitions while their heterozygous counterparts are slow progressers of the disease [3]. Cysteine-Cysteine Chemokine Receptor 5 (CCR5), referred to as CD195, is a component of the mammalian cell membrane and is receptor for chemokines that are activated during cell damage and inflammations This receptor is coded by a gene located in the human chromosome 3. The review considered studies conducted among general population, both HIV positive and HIV negative individuals, exposed seronegatives (ESN), exposed seropositives (ESP) and highly exposed seronegatives (HESN) and resultant data
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