The 3′UTR 1188 A/C polymorphism in the interleukin-12p40 gene (IL-12B) is associated with lepromatous leprosy in the west of Mexico

被引:28
作者
Alvarado-Navarro, Anabell [1 ]
Montoya-Buelna, Margarita [1 ]
Francisco Munoz-Valle, Jose [2 ]
Ivette Lopez-Roa, Rocio [1 ]
Guillen-Vargas, Cecilia [1 ]
Fafutis-Morris, Mary [1 ]
机构
[1] Univ Guadalajara, Ctr Univ Ciencias Salud, Dept Fis, Ctr Invest Inmunol & Dermatol, Guadalajara 44430, Jalisco, Mexico
[2] Univ Guadalajara, Ctr Univ Ciencias Salud, Inst Invest Reumatol & Sistema Musculo Esquelet, Guadalajara 44430, Jalisco, Mexico
关键词
IL-12; p40; polymorphism; leprosy;
D O I
10.1016/j.imlet.2008.03.015
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. IL-12 participates in the immune response against M. leprae by regulating T cell differentiation into the Th1-type response. Several single nucleotide polymorphisms have been identified in the IL-12 gene such as 3'UTR 1188 A/C polymorphism, which is associated with different diseases. However, the relationship of this polymorphism with the immune response in leprosy has not been explored. in this case-control study, we evaluated 44 patients with lepromatous leprosy (LL) and 51 healthy subjects (HS). We aimed to determine the relationship between 3'UTR 1188 A/C polymorphism of IL-12 p40, mRNA expression, and soluble IL-12 concentration in ILL patients and HS. Genotype frequencies were 41% A/A, 36% A/C, and 23% C/C in LL patients, and 47% A/A, 49% A/C, and 4% C/C in HS (p < 0.05). LL patients had a lower mRNA expression of IL-12 p40 gene, whereas HS had a higher expression level. Soluble IL-12 p40 concentration was higher in LL patients than in HS (p < 0.05). IL-12 p70 concentration did not differ between groups, and IL-12 p40 concentration was not significantly correlated with mRNA expression in either group. These data suggest that IL-12p403'UTR 1188 A/C polymorphism is associated with greater susceptibility to lepromatous leprosy in patients from western Mexico, independently of IL-12 p40 and p70 expression levels. (c) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:148 / 151
页数:4
相关论文
共 22 条
[1]   Antigen discovery:: a postgenomic approach to leprosy diagnosis [J].
Aráoz, R ;
Honoré, N ;
Cho, SG ;
Kim, JP ;
Cho, SN ;
Monot, M ;
Demangel, C ;
Brennan, PJ ;
Cole, ST .
INFECTION AND IMMUNITY, 2006, 74 (01) :175-182
[2]   Leprosy [J].
Britton, WJ ;
Lockwood, DNJ .
LANCET, 2004, 363 (9416) :1209-1219
[3]   Biosynthesis and posttranslational regulation of human IL-12 [J].
Carra, G ;
Gerosa, F ;
Trinchieri, G .
JOURNAL OF IMMUNOLOGY, 2000, 164 (09) :4752-4761
[4]  
CHOMCZYNSKI F, 1987, ANAL BIOCHEM, V162, P156
[5]   MOUSE INTERLEUKIN-12 (IL-12) P40 HOMODIMER - A POTENT IL-12 ANTAGONIST [J].
GILLESSEN, S ;
CARVAJAL, D ;
LING, P ;
PODLASKI, FJ ;
STREMLO, DL ;
FAMILLETTI, PC ;
GUBLER, U ;
PRESKY, DH ;
STERN, AS ;
GATELY, MK .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (01) :200-206
[6]   Genetic polymorphism of IL-12 p40 gene in immune-mediated disease [J].
Hall, MA ;
McGlinn, E ;
Coakley, G ;
Fisher, SA ;
Boki, K ;
Middleton, D ;
Kaklamani, E ;
Moutsopoulos, H ;
Loughran, TP ;
Ollier, WER ;
Panayi, GS ;
Lanchbury, JS .
GENES AND IMMUNITY, 2000, 1 (03) :219-224
[7]   Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit [J].
Huang, D ;
Cancilla, MR ;
Morahan, G .
GENES AND IMMUNITY, 2000, 1 (08) :515-520
[8]   Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome [J].
Keene, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) :7018-7024
[9]   Interferon-gamma differentially regulates interleukin-12 and interleukin-10 production in leprosy [J].
Libraty, DH ;
Airan, LE ;
Uyemura, K ;
Jullien, D ;
Spellberg, B ;
Rea, TH ;
Modlin, RL .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (02) :336-341
[10]  
Lopez-Roa Rocio Ivette, 2006, Rev Latinoam Microbiol, V48, P256