Lars Jørgen Østergaard

MCP1 SNPs and Pulmonary Tuberculosis in Cohorts from West Africa, the USA and Argentina: Lack of Association or Epistasis with IL12B Polymorphisms

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Digna R Velez Edwards
  • ,
  • Alessandra Tacconelli
  • ,
  • Philip C Hill
  • ,
  • Gerard A J Morris
  • ,
  • Todd L Edwards
  • ,
  • John R Gilbert
  • ,
  • Jamie L Myers
  • ,
  • Yo Son Park
  • ,
  • Martin E Stryjewski
  • ,
  • Eduardo Abbate
  • ,
  • Rosa Estevan
  • ,
  • Paulo Rabna
  • ,
  • Giuseppe Novelli
  • ,
  • Carol D Hamilton
  • ,
  • Richard Adegbola
  • ,
  • Lars Jørgen Østergaard
  • Scott M Williams
  • ,
  • William K Scott
  • ,
  • Giorgio Sirugo
  • ,
  • Christian Wejse
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.
Original languageEnglish
JournalPLOS ONE
Volume7
Issue2
Pages (from-to)e32275
ISSN1932-6203
DOIs
Publication statusPublished - 2012

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