title: MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and Argentina: lack of association or epistasis with IL12B polymorphisms.
abstract: 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.
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics and Miami Institute of Human Genomics, University of Miami, Miami, Florida, United States of America.
authors.forename: Digna R
authors.initials: DR
authors.lastname: Velez Edwards
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tacconelli
authors.forename: Christian
authors.initials: C
authors.lastname: Wejse
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: Gerard A J
authors.initials: GA
authors.lastname: Morris
authors.forename: Todd L
authors.initials: TL
authors.lastname: Edwards
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Myers
authors.forename: Yo Son
authors.initials: YS
authors.lastname: Park
authors.forename: Martin E
authors.initials: ME
authors.lastname: Stryjewski
authors.forename: Eduardo
authors.initials: E
authors.lastname: Abbate
authors.forename: Rosa
authors.initials: R
authors.lastname: Estevan
authors.forename: Paulo
authors.initials: P
authors.lastname: Rabna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Carol D
authors.initials: CD
authors.lastname: Hamilton
authors.forename: Richard
authors.initials: R
authors.lastname: Adegbola
authors.forename: Lars
authors.initials: L
authors.lastname: Østergaar
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sirugo
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000368:Aged; D001118:Argentina; D044383:Black People; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D004843:Epistasis, Genetic; D005006:Ethnicity; D005260:Female; D005714:Gambia; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006169:Guinea-Bissau; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000235:genetics*; D014481:United States; D044465:White People
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40