Genetic diversity and linkage disequilibrium in the chemokine receptor CCR2-CCR5 region among individuals and populations

Abstract

Background: Chemokine receptors CCR2 and CCR5 play a key role in immune and inflammatory responses and have been associated with several diseases, including AIDS. In order to comprehend health disparities it is important to understand the nature of genetic variation in specific genes of interest in different populations. Current studies of the CCR2 and CCR5 receptor genes are primarily focused on the CCR5-Δ32, and CCR2-V64I SNPs.

Methods: Sanger sequencing was used to sequence the regions containing 16 SNPs in the adjacent CCR2 and CCR5 genes (including CCR5-Δ32, and CCR2-V64I) in 249 subjects of African, European and Hispanic ancestry. Linkage disequilibrium (LD) and haplotypes were determined using Haploview.

Results: The data revealed large differences in allele frequencies of several SNPs and LD patterns among the ethnic groups, including SNPs that were restricted to Africans or Europeans. Seven known CCR5 haplotypes and six novel CCR2 haplotypes were identified. A rare case of an HIV+ subject with the CCR5-Δ32/Δ32 was identified.

Conclusions: These data demonstrate a LD between CCR2 and CCR5 at several loci and provide new information about CCR2 that contributes to our understanding of its population-specific genetic variability. The data indicate that in addition to CCR5-Δ32 and CCR2-V64I, other SNPs and haplotypes may be important genetic determinants of disease and should be investigated.

Keywords: CCR2; CCR5; Chemokine receptors; Ethnicity; Health disparities.

Fig 1

Genomic structure of the CCR2 and CCR5 genes. The location of genotyped SNPs are shown along the gene (see also Table 1).

Fig 2

Haploview generated linkage disequilibrium (LD) plots of 8 CCR2 SNPs #1–8) and 8 CCR5 SNPs (#9–16) in the post mortem brain sample from three ethnicities (A–C). Numbers in each box represent r² value and black squares represent r²=1. Squares go from dark to light to represent diminishing r² values.