Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

Samira H Al-Mahruqi,Fahad Zadjali,Albano Beja-Pereira,Crystal Y Koh,Ali A Al-Jabri,Abdullah Balkhair

doi:10.1590/s1415-47572014000100004

Samira H Al-Mahruqi, Fahad Zadjali + Show 4 more

Open Access

https://doi.org/10.1590/s1415-47572014000100004

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Abstract

Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%).

Highlights

The C-C motif chemokine receptor 5 (CCR5) is expressed in memory/effector T cells, monocytes/macrophages and immature dendritic cells (Oppermann, 2004)
We examined the frequency of the variable sites of the CCR5 gene and estimated the allele frequency of the V64I mutation in the CCR2 gene in the Omani population
There was high linkage disequilibrium (LD) between the single nucleotide polymorphisms (SNPs) in the CCR2-CCR5 gene locus and this allowed assessment of the diversity found in these two regions in 11 haplotypes

Summary

Introduction

The C-C motif chemokine receptor 5 (CCR5) is expressed in memory/effector T cells, monocytes/macrophages and immature dendritic cells (Oppermann, 2004). CCR5 is a co-receptor for human immunodeficiency virus-1 (HIV-1) that facilitates virus entry into cells and mediates infection (Littman, 1998; Mummidi et al, 1998). The CCR5 gene is located in the short arm of chromosome 3 and consists of four exons and two introns The P1 promoter gives rise to two full-length transcript variants while the P2 promoter results in several truncated transcripts that lack exon 1, all produce the same CCR5 protein (Mummidi et al, 2000; Wierda and van den Elsen, 2012)

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