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.