MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and Argentina: lack of association or epistasis with IL12B polymorphisms.

Velez Edwards DR, Tacconelli A, Wejse C, Hill PC, Morris GA, Edwards TL, Gilbert JR, Myers JL, Park YS, Stryjewski ME, Abbate E, Estevan R, Rabna P, Novelli G, Hamilton CD, Adegbola R, Ƙstergaar L, Williams SM, Scott WK, Sirugo G
PLoS One. 2012 7 (2): e32275

PMID: 22384203 · PMCID: PMC3288089 · DOI:10.1371/journal.pone.0032275

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (-2581A/G), rs2857656 (-362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility.

MeSH Terms (23)

Adolescent Adult African Americans African Continental Ancestry Group Aged Argentina Case-Control Studies Chemokine CCL2 Epistasis, Genetic Ethnic Groups European Continental Ancestry Group Female Gambia Genetic Predisposition to Disease Genetic Variation Guinea-Bissau Humans Interleukin-12 Subunit p40 Male Middle Aged Polymorphism, Genetic Tuberculosis, Pulmonary United States

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