Tag SNP polymorphism of CCL2 and its role in clinical tuberculosis in Han Chinese pediatric population

• Published in: PloS one 2011-02, Vol.6 (2), p.e14652-e14652
• Main Authors: Feng, Wei-Xing, Mokrousov, Igor, Wang, Bin-Bin, Nelson, Hugh, Jiao, Wei-Wei, Wang, Jing, Sun, Lin, Zhou, Si-Rui, Xiao, Jing, Gu, Yi, Wu, Xi-Rong, Ma, Xu, Shen, Adong
• Format: Article
• Language: English
• Subjects: Adolescent; Adults; Alleles; Amino acids; Antitubercular agents; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Bacillus Calmette-Guerin vaccine; BCG; Case-Control Studies; Cerebrospinal fluid; Chemokine CCL2 - genetics; Chemokines; Child; Child, Preschool; Children; Children & youth; China - ethnology; Cytokines; Drosophila; Ethnic Groups - genetics; Family planning; Female; Gene expression; Gene polymorphism; Genes; Genetic aspects; Genetics and Genomics/Genetics of Disease; Genetics and Genomics/Genetics of the Immune System; Genotypes; Granuloma; Haplotypes; Haplotypes - genetics; Health aspects; Health risks; Hospitals; Humans; Immunity; Immunology/Immune Response; Infections; Infectious Diseases/Respiratory Infections; Innate immunity; Insects; Leukocytes; Linkage Disequilibrium - genetics; Male; Males; Meningitis; Monocyte chemoattractant protein 1; Mutation; Mycobacterium tuberculosis; Nervous system; Pediatric diseases; Pediatrics; Phenotype; Polymorphism; Polymorphism, Single Nucleotide - genetics; Population genetics; Proteins; Risk factors; Sex Characteristics; Signaling; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Tuberculosis; Tuberculosis, Meningeal - genetics; Tuberculosis, Pulmonary - cerebrospinal fluid; Tuberculosis, Pulmonary - complications; Tuberculosis, Pulmonary - genetics; Vaccination
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014652

Chemokine (C-C motif) ligand 2 CCL2/MCP-1 is among the key signaling molecules of innate immunity; in particular, it is involved in recruitment of mononuclear and other cells in response to infection, including tuberculosis (TB) and is essential for granuloma formation. We identified a tag SNP for the CCL2/MCP-1 gene (rs4586 C/T). In order to understand whether this SNP may serve to evaluate the contribution of the CCL2 gene to the expression of TB disease, we further analysed distribution of its alleles and genotypes in 301 TB cases versus 338 non-infected controls (all BCG vaccinated) representing a high-risk pediatric population of North China. In the male TB subgroup, the C allele was identified in a higher rate (P = 0.045), and, acting dominantly, was found to be a risk factor for clinical TB (P = 0.029). Homozygous TT genotype was significantly associated with lower CSF mononuclear leukocyte (ML) counts in patients with tuberculous meningitis (TBM) (P = 0.001). The present study found an association of the CCL2 tag SNP rs4586 C allele and pediatric TB disease in males, suggesting that gender may affect the susceptibility to TB even in children. The association of homozygous TT genotype with decreased CSF mononuclear leukocyte (ML) count not only suggests a clinical significance of this SNP, but indicates its potential to assist in the clinical assessment of suspected TBM, where delay is critical and diagnosis is difficult.