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

Centro de Investigación en Inmunología y Dermatología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Immunology Letters (Impact Factor: 2.51). 06/2008; 118(2):148-51. DOI: 10.1016/j.imlet.2008.03.015
Source: PubMed


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 LL 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-12 p40 3'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.

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    • "Primers 5′-TTT CTG TTA TTA ACA AAC ATC ACT CTG-3′ and 5′-CAA CAC TTG TAC ATA TTT TTA TTC AAt AT-3′ (mismatch is shown in bold lower case) were used for rs56245420. Other five SNPs were genotyped by PCR-RFLP methods described previously with slight modification [11–15]. PCR reaction was carried out in a total volume of 20 μL containing 20 ng of genomic DNA, 1 × PCR buffer, 1.5 mM MgCl2, 200 μM of each dNTP, 30 ng of each primer, and 1 unit of Taq DNA polymerase (TakaRa). "
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    • "The complex genetic regulation of the adaptive immune response resulting from the balance between different secreted cytokines is crucial for the outcome of the host-pathogen interactions, that is, elimination of the bacilli, development of the resistant form of leprosy (TT), or the more severe form (LL). This has been confirmed by the observation that polymorphisms of key cytokines genes, such as TNF (Santos et al. 2002; Sapkota et al., 2010; Cardoso et al. 2011), IL-12 (Alvarado-Navarro et al. 2008), IL-4 (Yang et al. 2011; Sampaio et al. 2012), IL-10, TGF-B, IL-6, and their respective receptors (Aggarwal et al. 2011) have been associated with susceptibility to and severity of leprosy. HLA-related gene polymorphisms have also been investigated in adaptive immunity against leprosy. "
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    • "In Western Mexico, Alvarado-Navarro et al. [61] found that the 1188A/C polymorphism in the 3′UTR of IL12p40 gene was associated with greater susceptibility to lepromatous leprosy, independent of the expression levels of IL-12 p40. Conversely, Jesús Salvador et al. [62] in a study with Mexican patients found no significant association between genotype and allele frequencies of the 1188A/C polymorphism and lepromatous leprosy [62]. "
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