CCL3L1 copy number, CCR5genotype and susceptibility to tuberculosis

Abstract

BackgroundTuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB.Methods and resultsCopy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48).ConclusionsThe case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

The variations of IL-23R are associated with susceptibility and severe clinical forms of pulmonary tuberculosis in Chinese Uygurs

“…It suggested that the CNV was an independent risk factor for pulmonary TB in contrast with SNPs among Chinese Uygurs. However, a recent study found that there was an association of CCL3L1 copy number with TB in a northwestern Colombian population [ 31 ], but not in African and Peruvian populations [ 32 ]. All these data indicate that CNVs in some special genes may also be associated with susceptibility to TB, although the ethnic difference exists.…”

CCL5 rs2107538 Polymorphism Increased the Risk of Tuberculosis in a Sample of Iranian Population

“…They observed that -403G/G and -28C/C genotypes as well as -403G allele and -28C allele were significantly more frequent in control subjects. Carpenter et al (2014) didn't find any association between CCR5 polymorphism and susceptibility to clinically active TB. Mishra et al (2012) have found no significant association between CCR5 polymorphism with either resistance or susceptibility to TB in Sahariya tribe of north central India population.…”

“…CCR5 Δ32 is a deletion of gene results in a non-functional receptor form of the chemokine receptor that is unable to bind CC chemokine ligands such as CCL5. Numerous studies have shown the association of CCL5 and CCR5 gene polymorphism and the risk of TB in various ethnic populations, but the results were controversial (Ben-Selma et al, 2011;Selvaraj et al, 2011;Carpenter et al, 2014). Therefore, the present case-control study was designed to investigate the possible association between CCL5 -403G/A (rs2107538), CCL5 -28C/G (rs2280788) and CCR5 Δ32 polymorphisms and pulmonary tuberculosis in a sample of southeast Iranian population.…”

“…CCR5 or CD195 is a member of the beta chemokine receptor family. This protein is expressed by T-cells, macrophages, immature dendritic cells and granulocytes and has an important role in inflammatory response to infection (Carpenter et al, 2014). It has been reported that CCR5 is overexpressed in PTB (pulmonary tuberculosis) patients in comparison with normal subjects (Mamtani et al, 2011).…”

Effects of CCR5 59029G/A polymorphism on the risk to diabetic nephropathy

“…The gene CCR5 is polymorphic and located within the gene cluster on chromosome 3p21.3-p24 [ 17 ]. The polymorphisms in this gene may affect the activity of the protein, thus contributing to multiple diseases, including HIV-1 infection [ 18 ], cancers [ 19 ], tuberculosis [ 20 ], atopic asthma [ 21 ] and DN [ 22 ].…”