• Resp Res · Jan 2011

    Multicenter Study

    A promoter SNP rs4073T>A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode.

    • Mi-Hyun Ahn, Byung-Lae Park, Shin-Hwa Lee, Sung-Woo Park, Jong-Sook Park, Do-Jin Kim, An-Soo Jang, Jai-Soung Park, Hwa-Kyun Shin, Soo-Taek Uh, Yang-Ki Kim, Young Whan Kim, Sung Koo Han, Ki-Suck Jung, Kye Young Lee, Sung Hwan Jeong, Jeong Woong Park, Byoung Whui Choi, In Won Park, Man Pyo Chung, Hyoung Doo Shin, Jin Woo Song, Dong Soon Kim, Choon-Sik Park, and Young-Soo Shim.
    • Div of Allergy and Respiratory Medicine, Dept of Internal Medicine, Soonchunhyang Univ, Bucheon Hospital, 1174 Jung-dong, Wonmi-gu, Bucheon 420-020, Korea.
    • Resp Res. 2011 Jan 1;12:73.

    BackgroundInterleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF.MethodsOne promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay.ResultsThe minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002).ConclusionThe common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

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