Association of tumor necrosis factor-α-308G/A and interleukin-6-174G/C gene polymorphisms with the susceptibility of respiratory syncytial virus bronchiolitis
ZHANG Ya-Li, DONG Lin, CHEN Xiao-Fang.
Department of Pulmonary, Yuying Children′s Hospital Affiliated to Wenzhou Medical College, Wenzhou, Zhejiang 325027, China.
Abstract OBJECTIVE: To study the association of tumor necrosis factor (TNF)-α-308G/A and interleukin (IL)-6-174G/C gene polymorphisms with the susceptibility of respiratory syncytial virus (RSV) bronchiolitis. METHODS: Polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) was used to identify the polymorphisms at position 308 of the TNF-α promoter and -174 of the IL-6 promoter in 150 children with RSV bronchiolitis and 120 healthy children (control group). RESULTS: The frequency of GG, GA and AA genotypes of TNF-α-308 was 68.0%, 28.0% and 4.0% respectively in the RSV group, while that was 80.8%, 19.2% and 0 respectively in the control group. There were significant differences in the genotype frequencies between the two groups (χ2=5.665, P<0.05). The frequency of G and A alleles in the RSV group was 82.0% and 18.0% respectively, while that was 90.4% and 9.6% respectively in the control group. The frequency of A allele in the RSV group was significantly higher than that in the control group (χ2=7.726, P<0.05). Compared to the children carrying G allele, the children with A allele demonstrated a 2.071-fold increased risk of RSV bronchiolitis (OR=2.071, P<0.05). Only GG genotype was detected at position -174 of IL-6 in both groups. CONCLUSIONS: TNF-α-308A is associated with the susceptibility of RSV bronchiolitis and it might be an important candidate gene for the development of RSV bronchiolits. IL-6-174G/C gene polymorphism is not found in children in Wenzhou area.[Chin J Contemp Pediatr, 2009, 11 (10):821-824]
ZHANG Ya-Li,DONG Lin,CHEN Xiao-Fang. Association of tumor necrosis factor-α-308G/A and interleukin-6-174G/C gene polymorphisms with the susceptibility of respiratory syncytial virus bronchiolitis[J]. 中国当代儿科杂志, 2009, 11(10): 821-824.
ZHANG Ya-Li,DONG Lin,CHEN Xiao-Fang. Association of tumor necrosis factor-α-308G/A and interleukin-6-174G/C gene polymorphisms with the susceptibility of respiratory syncytial virus bronchiolitis[J]. CJCP, 2009, 11(10): 821-824.
[1]McNamara PS, Flanaqan BF, Selby AM, Hart CA, Smyth TL. Pro- and anti-inflammatory responses in respiratory syncytial virus bronchiolitis[J]. Eur Respir J, 2004, 23(1):106-112.
[2]Matsuda K, Tsutsumi H, Okamoto Y, Chiba C. Development of interleukin-6 and tumor necrosis factor alpha activity in nasopharyngeal secretions of infants and children during infection with respiratory syncytial virus[J]. Clin Diag Lab Immunol, 1995, 2(3):322-324.
[5]Louis E, Franchimont D, Prion A, Gevaert Y, SchaafLafontaine N, Roland S, et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)stimulated whole blood cell culture in healthy humans[J]. Clin Exp Immunol, 1998, 113(3):401-406.
[6]Schaaf BM, Seitzer U, Pravica V, Aries SP, Zabel P. Tumor necrosis factor-alpha -308 promoter gene polymorphism and increased tumor necrosis factor serum bioactivity in farmer′s lung patients[J]. Am J Respir Crit Care Med, 2001, 163(2):379-382.
[7]Kumar V, Khosla R, Gupta V, Ssrin BC, Sehajpal PK. Differential association of tumour necrosis factor-alpha single nucleotide polymorphism (308) with tuberculosis and bronchial asthma[J]. Natl Med J India, 2008, 21(3):120-122.
[8]Hoebee B, Bont L, Rietveld E, van Oosten M, Hodemaekers HM, Naqelkerke NJ, et al. Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-α genes on respiratory syncytial virus bronchiolitis[J]. J Infect Dis, 2004, 189(5):239-247.
[9]Talar-Wojnarowska R, Gasiorowska A, Smolarz B, Romanowicz-Makowska H, Kuliq A, Malecka-Panas E. Clinical significance of interleukin-6 (IL-6) gene polymorphism and IL-6 serum level in pancreatic adenocarcinoma and chronic pancreatitis[J]. Dig Dis Sci, 2009, 54(3):683-689.
[10]Gentile DA, Doyle WJ, Zeevi A, Howe-Adams J, Kapadia S, Trecki J, et al. Cytokine gene polymorphisms moderate illness severity in infants with respiratory syncytial virus infection[J]. Hum Immunol, 2003, 64(3):338-344.
[11]Zhai R, Liu G, Yang C. The G to C polylmorphism at -174 of the interleukin-6 gene is rare in Southern Chinese population[J]. Pharmacogenetics, 2001, 11(8):899-701.
[12]Ota N, Nakajima T, Nakazawa I, Suzuki T, Hosoi T, Orimo H, et al. A nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density[J]. Hum Genet, 2001, 46(5):267-272.
[13]Lim CS, Zheng S, Kim YS, Ahn C, Han JS, Kim S, et al. The-174 G to C polymorphism of interleukin-6 gene is very rare in Koreans[J]. Cytokine, 2002, 19(10):52-54.