Influence of nucleotide polymorphisms in the CCR2 gene and the CCR5 promoter on the expression of cell surface CCR5 and CXCR4

Polymorphisms in the CCR2 gene (CCR2-64I) and the CCR5 promoter (pCCR5-5902 9G) have been correlated with slower HIV-1 disease progression. How these p olymorphisms influence the rate of AIDS progression has remained unclear. W e have therefore investigated whether these nucleotide polymorphisms will r educe the expression levels of surface CCR5 and CXCR4, and thus lead to slo wer AIDS progression. For this, a cohort of Chinese volunteers in Taiwan wa s subjected to the determination of CCR2 and pCCR5 genotypes followed by an alysis of the surface CCR5 and CXCR4 expression on five cell types derived from peripheral blood mononuclear cells by flow cytometry. Several signific ant associations were detected between genotypes and expression levels of t he proteins, The most important finding was that an increased number of CD4 (+) cells expressing CCR5 correlated with pCCR5-59029A homozygosity without the interference of both the CCR2-64 and the CCR5 Delta 32 (deleted 32 bp) mutations (P = 0.0453), which is consistent with the previous data on the association of the genotype to AIDS progression, Since different genetic po lymorphisms co-exist in human beings, the rate of AIDS progression as well as the risk of rheumatoid arthritis may be governed by the interplay of the array of nucleotide changes and their affected proteins.