A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis

被引:211
作者
Flores-Villanueva, PO [1 ]
Ruiz-Morales, JA
Song, CH
Flores, LM
Jo, EK
Montaño, M
Barnes, PF
Selman, M
Granados, J
机构
[1] Univ Texas Hlth Ctr, Ctr Biomed Res, Tyler, TX 75708 USA
[2] Chungnam Natl Univ, Coll Med, Dept Microbiol, Taejon 301747, South Korea
[3] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA
[4] Mexican Inst Resp Dis, Mexico City 14080, DF, Mexico
[5] Mexican Natl Inst Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14000, DF, Mexico
关键词
D O I
10.1084/jem.20050126
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We examined the distribution of single nucleotide polymorphisms ( SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein-1 alpha genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti-MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis - stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis - stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.
引用
收藏
页码:1649 / 1658
页数:10
相关论文
共 60 条
[41]   Monocyte chemoattractant protein-1 selectively inhibits, the acquisition of CD40 ligand-dependent IL-12-producing capacity of monocyte-derived dendritic cells and modulates Th1 immune response [J].
Omata, N ;
Yasutomi, M ;
Yamada, A ;
Iwasaki, H ;
Mayumi, M ;
Ohshima, Y .
JOURNAL OF IMMUNOLOGY, 2002, 169 (09) :4861-4866
[42]   Novel human immunodeficiencies reveal the essential role of type-1 cytokines in immunity to intracellular bacteria [J].
Ottenhoff, THM ;
Kumararatne, D ;
Casanova, JL .
IMMUNOLOGY TODAY, 1998, 19 (11) :491-494
[43]   Use of unlinked genetic markers to detect population stratification in association studies [J].
Pritchard, JK ;
Rosenberg, NA .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (01) :220-228
[44]  
Reich DE, 2001, GENET EPIDEMIOL, V20, P4, DOI 10.1002/1098-2272(200101)20:1<4::AID-GEPI2>3.0.CO
[45]  
2-T
[46]   Association between tuberculosis and a polymorphic NFκB binding site in the interferon γ gene [J].
Rossouw, M ;
Nel, HJ ;
Cooke, GS ;
van Helden, PD ;
Hoal, EG .
LANCET, 2003, 361 (9372) :1871-1872
[47]   A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression [J].
Rovin, BH ;
Lu, L ;
Saxena, R .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 259 (02) :344-348
[48]  
RUTLEDGE BJ, 1995, J IMMUNOL, V155, P4838
[49]  
Ryu S, 2000, INT J TUBERC LUNG D, V4, P577
[50]   A prospective study of bacillus Calmette-Guerin scar formation and tuberculin skin test reactivity in infants in Lima, Peru [J].
Santiago, EM ;
Lawson, E ;
Gillenwater, K ;
Kalangi, S ;
Lescano, AG ;
Du Quella, G ;
Cummings, K ;
Cabrera, L ;
Torres, C ;
Gilman, RH .
PEDIATRICS, 2003, 112 (04) :E298-E302