Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy

Abstract

BACKGROUND AND OBJECTIVES:Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses.METHODS:We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens.RESULTS:From a panel of ten known SNPs, only three polymorphisms: –G190A in CCR2, –T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy.CONCLUSION:The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR5Δ32 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the –G190A mutation in the CCR2 receptor gene.

Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?

“…These results are in contrast with the Bogdanski et al study [39] who demonstrated that CCR5 expression is increased on immune cells in T2D [39]. Due to the fact that CCR5 Δ 32 mutation leads to [5,8,9]. In summary, an increased expression of CCR5 on immune cells of T2D patients with and without nephropathy was reported by several researchers [38,39].…”

“…It has been shown that chemokines play key roles in the regulation of immune responses which are important in the pathogenesis of both autoimmunity-and hypersensitivity-based diseases [4]. Chemokine receptor 5 (CCR5) is located on the short arm of chromosome 3 (3p21.31), which is a locus for multiple chemokine receptor genes [5]. CCR5 is a receptor for the MIP-1α/ CCL3, MIP-1β/CCL4, and RANTES/CCL5 chemokines and is expressed by several immune cells including NK cells, T lymphocytes, macrophages, and immature dendritic cells and is upregulated by proinflammatory cytokines [6,7] as well as nuclear factor kappa-lightchain-enhancer (NF-κB) [8].…”

The Chemokine Receptor 5 Delta32 Polymorphism and Type 1 Diabetes, Behcet’s Disease, and Asthma: A Meta-analysis

“…However, 5 of these 17 articles were excluded, 2 because they did not investigate the CCR5 polymorphism (Bettencourt et al, 2010;Mlynarski et al, 2005), and 3 because they were family based studies (Al-Abdulhadi & Al-Rabia, 2010, Al-Abdulhadi & Al-Rabia, 2011Mitchell et al, 2000). One eligible study contained data on 3 different BD groups, and these were treated independently (X. .…”

“…We identified 84 articles by electronic and manual searching, and 17 were selected for a full-text review based on title and abstract details (Abousaidi et al, 2011;Al-Abdulhadi & Al-Rabia, 2010;Al-Abdulhadi & Al-Rabia, 2011;Atzeni et al, 2012;Bettencourt et al, 2010;Dhaouadi et al, 2013;Gambelunghe et al, 2003;Kalev et al, 2003;Maier-Moore et al, 2013;Mitchell et al, 2000;Mlynarski et al, 2005;Mojtahedi et al, 2006;Sandford et al, 2001;Smyth et al, 2008;Szalai et al, 1999;B. Yang et al, 2004, X. Yang et al, 2004.…”

HIV-1 Infection: The Functional Importance of SDF1, CCR2 and CCR5 in Protection and Therapeutics

“…CCR2 located on chromosome 3p21 is an important entry coreceptor for HIV1 virus infecting host CD4+ cells [9]. Presence of 64Valine to Isolucine mutation in the coding region of this gene has been credited for delaying disease progression that is supported by stable or decreased viral loads and showed decline in CD4+ cells populations in HIV1 infected patients.…”