1Microbiology Department, Islamic Azad University, Jahrom, Iran.
2Immunology Department, Prof. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3Microbiology Department, Fasa University of Medical Sciences, Fasa, Iran.
4Microbiology Department, Fasa University of Medical Sciences, Fasa, Iran.
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
5Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
چکیده
Brucella is an intracellular Gram-negative bacterium. Previous reports showed that gene polymorphisms of cytokines can affect resistance or susceptibility to Brucella infection. Interleukin-13, a cytokine secreted by Th2 lymphocytes, has an important role in immune responses against established infections. In this study, we investigated the association of three polymorphic sites of IL-13 with susceptibility to brucellosis in Iranian population. In this study 169 patients with brucellosis and 71 healthy controls were included. DNA was extracted and genotyped for three bi-allelic polymorphisms of IL-13 gene at positions -1512A/C, -1055C/T, and +2044G/A by polymerase chain reaction-restriction fragment length polymorphism method. None of the studied alleles and genotypes of IL-13 gene (-1512A/C, -1055C/T, and +2044G/A) showed significant relationship with susceptibility to brucellosis. However, among eight haplotypes, the distribution of TCG and CAA haplotypes were significantly higher in the patients compared with those in the controls (P=0.002 and P=0.034, respectively). Although, the later did not tolerate Bonferroni correction. On the contrary, the distribution of TCA haplotype was higher in the controls compared to that in the patients (P=0.01). Furthermore, TAG/TCA haplogenotypes were significantly higher among controls compared to the brucellosis patients (P=0.025). P value resulted from TCA and TAG/TCA did not tolerate Bonferroni correction. There is no association between the inheritance of different alleles and genotypes of interleukin-13 gene and susceptibility to brucellosis. However, it seems that the inheritance of some haplotypes and haplogenotypes of IL-13 can impact the susceptibility to brucellosis.
Golding B, Scott DE, Scharf O et al (2001) Immunity and protection against Brucella abortus. Microbes Infect. 3(1):43-8
Rodriguez-Zapata M, Matias MJ, Prieto A et al (2010) Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function. Infect Immun. 78(7): 3272â3279
Skendros P, Pappas G, Boura P (2011) Cell-mediated immunity in human brucellosis. Microbes Infect. 13(2):134-42
Moreno-Lafont MC, Lopez-Santiago R, Paredes-Cervantes V et al (2003) Activation and proliferation of T lymphocyte subpopulations in patients with brucellosis. Archives of medical research. 34(3):184-93
Akbulut H, Celik I, Akbulut A (2007) Cytokine levels in patients with brucellosis and their relations with the treatment. Indian J Med Microbiol. 25(4):387-90
Refik M, Mehmet N, Durmaz R et al (2004) Cytokine profile and nitric oxide levels in sera from patients with brucellosis. Braz J Med Biol Res. 37(11):1659-63
Koen V (2006) Cytokine gene polymorphism in multifactorial conditions. Taylor & Francis Group. pp 83-93
Moravej A, Rasouli M, Kalani M et al (2012) IL-1β (-511T/C) gene polymorphism not IL-1β (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis. Mol Biol Rep. 39(6):6907-14
Kalani M, Rasouli M, Moravej A et al (2011) Association of interleukin-15 single nucleotide polymorphisms with resistance to brucellosis among Iranian patients. Tissue Antigens. 78(5):352-8
Rasouli M, Kalani M, Moravej A et al (2011) Interleukin-18 single nucleotide polymorphisms contribute to the susceptibility to brucellosis in Iranian patients. Cytokine 54(3):272-6
Karaoglan I, Pehlivan S, Namiduru M et al (2009) TNF-α, TGF-β, IL-10, IL-6 and IFN-γ gene polymorphisms as risk factors for brucellosis. New Microbiol. 32(2):173-8
Tarazona-Santos E, Tishkoff S (2004) Divergent patterns of linkage disequilibrium and haplotype structure across global populations at the interleukin-13 (IL13) locus. Genes and immunity 6(1):53-65
Wills-Karp M (2000) The gene encoding interleukin-13: a susceptibility locus for asthma and related traits. Respiratory research 1(1):19
Van der Pouw KT, Van Veen A, Boeije L et al (1999) An IL-13 promoter polymorphism associated with increased risk of allergic asthma. Genes and immunity 1(1):61.
Izuhara K, Arima K (2004) Signal transduction of IL-13 and its role in the pathogenesis of bronchial asthma. Drug News Perspect 17:91â98 doi:10.1358/dnp.2004.17.2.829041
Van der Pouw Kraan TC, van Veen A, Boeije LC et al (1999) An IL-13 promoter polymorphism associated with increased risk of allergic asthma. Genes Immun. 1:61â65. doi:10.1038/sj.gene. 6363630
Ohashi J, Naka I, Patarapotikul J et al (2003) A single-nucleotide substitution from C to T at position -1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand. Genes Immun. 4:528â531. doi:10.1038/sj.gene.6364010
Noguchi E, Nukaga-Nishio Y, Jian Z et al (2001) Haplotypes of the 5 region of the IL-4 gene and SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma. Hum Immunol. 62:1251â1257. doi:10.1016/S0198-8859 (01)00338-X
Howard TD, Whittaker PA, Zaiman AL et al (2001) Identiïcation and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population. Am J Respir Cell Mol Biol. 25:377â384
Heinzmann A, Mao XQ, Akaiwa M et al (2000) Genetic variants of IL-13 signaling and human asthma and atopy. Hum Mol Genet. 9:549â559. doi:10.1093/hmg/9.4.549
Excofïer L, Laval G, Schneider S (2005) Arlequin ver. 3.1: an integrated software package for population genetics data analysis. Evol Bioinform Online 1:47â50
Gong Y, Shi GC, Wan HY et al (2013) Association between the interleukin-13 gene and development of chronic obstructive pulmonary disease in southern Chinese Han population: a case-control study. Chin Med J. 126(23):4403-8.
Shazia M, Kanza M, Mehwish I et al (2013) IL-13 gene polymorphisms and their association with atopic asthma and rhinitis in Pakistani patients. Iran J Allergy Asthma Immunol. 28;12(4):391-6
Okeyo WA, Munde EO, Okumu W et al (2013) Interleukin (IL)-13 promoter polymorphisms (-7402 T/G and -4729G/A) condition susceptibility to pediatric severe malarial anemia but not circulating IL-13 levels. BMC Immunol. 25;14:15. doi: 10.1186/1471-2172-14-15