Influence of Variations in CCL3L1 and CCR5 on Tuberculosis in a Northwestern Colombian Population

Mamtani, Manju; Mummidi, Srinivas; Ramsuran, Veron; Pham, Minh Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; Ndung’u, Thumbi; He, Weijing; Anaya, Juan Manuel; Ahuja, Sunil K.

doi:10.1093/infdis/jir145

Cited by 27 publications

(28 citation statements)

References 16 publications

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“…However, surprisingly the association studies of CCL3L1 / CCL4L1 copy number provide no evidence for an association of copy number with clinically active TB in all three populations. A previous study (n = 298) found evidence individuals with CCL3L1 copy numbers greater than the average (CN = 2) were associated with increased susceptibility to active TB in a Colombian population [24]. However our study could not replicate this observation in Peruvian samples despite the greater sample size.…”

Section: Discussioncontrasting

confidence: 75%

“…The correlation of variants in the chemokine-chemokine receptor pair with TB susceptibility may have been anticipated from functional analyses, but our data does not support this. A recent observation identified that haplotypes in CCR5 associated with increased expression of CCR5 are associated with TB susceptibility in individuals with 2 copies or more of CCL3L1 [24]. Our understanding of the precise role of cytokines in TB infection remains limited (reviewed in [43]) and there is much compensation and overlap of roles due to the complexity of the system.…”

Section: Discussionmentioning

confidence: 99%

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CCL3L1 copy number, CCR5genotype and susceptibility to tuberculosis

et al. 2014

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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.

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

CCL3L1 copy number, CCR5genotype and susceptibility to tuberculosis

et al. 2014

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“…Chemokines are a family of small (8)(9)(10) proteins that have the ability to attract and activate leukocytes. The biological activities of chemokines are mediated by interactions with their cell-surface receptors that belong to the structurally related seven-transmembrane domain superfamily of proteins [5].…”

Section: Introductionmentioning

confidence: 99%

“…The expression levels of chemokines and their receptors have been found associated with infectious and autoimmune diseases. In recent years, it has been described genetic polymorphisms that affect the levels of expression, and some of them were associated with susceptibility, progression and severity to certain diseases [6][7][8][9]. Moreover, exist experimental evidence that suggest that chemokine and chemokine receptors may contribute to cardiac tissue damage during Chagas disease [10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in the chemokines and chemokine receptors in Chagas disease

Flórez¹,

Martín²,

González³

2012

Human Immunology

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“…Mamtani et al (2011) evaluated the effects of CCR5 haplotypes (including CCR5∆32 and eight other CCR5 variants) on tuberculosis in Colombian individuals (Mamtani et al, 2011; Mummidi et al, 2000). The haplotype CCR5 ‐HHD (in which CCR5∆32 wild‐type allele is present; see Table 1 for complete haplotype description) was associated with increased CCR5 expression and was considered a risk factor for tuberculosis (Mamtani et al, 2011).…”

Section: Ccr5 and Ccr5δ32 In Bacterial Infectionsmentioning

confidence: 99%

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

Ellwanger

Kaminski

Rodrigues

et al. 2020

Int J Immunogenetics

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The CCR5 molecule was reported in 1996 as the main HIV‐1 co‐receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV‐1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the “renaissance of CCR5 research,” this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

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Influence of Variations in CCL3L1 and CCR5 on Tuberculosis in a Northwestern Colombian Population

Cited by 27 publications

References 16 publications

CCL3L1 copy number, CCR5genotype and susceptibility to tuberculosis

CCL3L1 copy number, CCR5genotype and susceptibility to tuberculosis

Genetic variants in the chemokines and chemokine receptors in Chagas disease

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

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