title: Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population.
abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for association with TB in a Northeastern Brazilian population (295 subjects, 131 TB patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated with susceptibility to TB, and in particular with pulmonary and extra-pulmonary forms respectively. The -871A>G and -336A>G SNPs were associated, the first with protection to both pulmonary and extra-pulmonary TB, the latter only with the pulmonary form. An association between GGAG haplotype and protection to TB infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was associated with TB infection. This study provides evidence of an association between CD209 and CD209L polymorphisms and TB development in a Brazilian population, suggesting that variations in these genes may influence the protection and susceptibility to infection caused by M. tuberculosis.
authors.affiliation: Department of Genetics, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife, PE, Brazil, ronaldocelerino@yahoo.com.br.
authors.forename: Ronaldo Celerino
authors.initials: RC
authors.lastname: da Silva
authors.forename: Ludovica
authors.initials: L
authors.lastname: Segat
authors.forename: Heidi Lacerda Alves
authors.initials: HL
authors.lastname: da Cruz
authors.forename: Haiana Charifker
authors.initials: HC
authors.lastname: Schindler
authors.forename: Lilian Maria Lapa
authors.initials: LM
authors.lastname: Montenegro
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Rafael Lima
authors.initials: RL
authors.lastname: Guimarães
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics*; D055815:Young Adult; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human