Systematic meta-analysis of the association between monocyte chemoattractant protein-1 -2518A/G polymorphism and risk of tuberculosis

Abstract

ABSTRACT. Numerous studies have been conducted to investigate the association between 2518A/G polymorphisms in the monocyte chemoattractant protein-1 (MCP-1) gene and the risk of tuberculosis (TB). However, the results have been inconsistent and inconclusive. In this study, we performed a meta-analysis to evaluate the association between the MCP-1 -2518A/G polymorphism and TB. The National Center for Biotechnology Information Global Cross Database and Google Scholar database were searched for relative studies. A total of 22 case-control studies that included 7332 cases and 8004 controls for the -2518A/G single-nucleotide polymorphism were identified. The results revealed an association between the MCP-1 -2518A/G polymorphism and human TB susceptibility under a recessive model (GG vs GA+AA), dominant model (GG+GA vs AA), and homozygote comparison (GG vs AA) model for the entire database. For the dominant model, the overall odds ratio was 1.34 (95% confidence interval, 1.10-1.64, P = 0.004). For the recessive model, the overall odds ratio was 1.46 (95% confidence interval, 1.15-1.86, P = 0.002). For the homozygote comparison, the overall odds ratio was 1.67 (95% confidence interval, 1.20-2.32, P = 0.002). In the subgroup analysis by ethnicity, significantly elevated risks were found in Asians and Americans, but not in Africans and Europeans. We also used the Begg and Egger tests to examine publication bias, and no major publication bias was detected. Our results indicate that there is an association between the MCP-1 -2518A/G polymorphism and human TB susceptibility.

A novel role for C–C motif chemokine receptor 2 during infection with hypervirulent Mycobacterium tuberculosis

“…However, since CCL2 −/− mice did not fully reflect the heightened susceptibility of the CCR2 −/− mice to HN878 infection, other ligands such as CCL7 and CCL12 may mediate CCR2 driven protection during Mtb HN878 infection. Given the relevance of CCL2 in human disease 4,19 , we chose to focus on CCL2 production in subsequent experiments. To determine the main cellular sources of CCL2 upon infection, we assessed CCL2 levels in supernatants of lung epithelial cells, DCs,and macrophages after in vitro infection with either H37Rv or HN878.…”

“…In humans, polymorphisms in CCL2 have been associated with pulmonary TB 4 , while mouse infection studies have shown that CCR2 expression is dispensable for protective immunity to infection with aerosolized Euro-American lineage 4 Mtb strains 1 . Zebrafish modeling of granulomas using M. marinum has proposed that the CCR2-CCL2 axis through interactions with virulence factors drives the generation of permissive macrophages and promotes mycobacterial replication and pathogenesis 7 .…”

“…A major ligand for CCR2 is C-C motif chemokine ligand 2 (CCL2), along with the ligands CCL7 and CCL12. In human populations, meta-analysis of the identified −2518 A/G single nucleotide polymorphism (SNP) in the promoter region of the CCL2 gene show significantly elevated risk for pulmonary TB 4 . Recent studies have highlighted differences in cytokine induction and immune requirements for Mtb control to be dependent on the infecting Mtb strain 5,6 .…”

Current immunogenetic predisposition to tuberculosis in the Moroccan population

“…More than nine genetic polymorphisms have been identified in the coding region and MCP‐1 promoter, although it would seem that only the MCP‐1 −2518 A/G allele has a significant, functional effect at gene expression level (Flores‐Villanueva et al., ). The MCP‐1 −2518 G allele was found to be associated with an increased susceptibility to TB in most of the cases (Feng et al., ; Flores‐Villanueva et al., ; Ganachari et al., ; Shi, Yang, Sun, Yin, & Song, ; Tian, Li, Li, Wang, & Cheng, ). The homozygous MCP‐1‐2518 G allele has been reported to be less common in Moroccan and Ghanaian TB patients than it is in healthy controls (Arji et al., ; Thye et al., ).…”

“…Finally, meta‐analysis studies revealed that the MCP‐1‐2518G allele increased the risk of developing TB for Asians and Hispanics, but not for Africans (Feng et al., ; Tian et al., ; Zhang et al., ). More recently, these data have been well supported by the Vásquez‐Loarte meta‐analysis study; however, the authors stressed that this genetic analysis results were influenced significantly by the ethnicity of the study's subjects, as the MCP‐1‐ 2518G allele may not be associated with some Asian groups, such as those from India and Persia (Vásquez‐Loarte, Trubnykova, & Guio, ).…”