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

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Ahn, Mi-Hyun; Park, Byung-Lae; Lee, Shin-Hwa; Park, Sung-Woo; Park, Jong-Sook; Kim, Do-Jin; Jang, An-Soo; Park, Jai-Soung; Shin, Hwa-Kyun; Uh, Soo-Taek; Kim, Yang-Ki; Kim, Young Whan; Han, Sung Koo; Jung, Ki-Suck; Lee, Kye Young; Jeong, Sung Hwan; Park, Jeong Woong; Choi, Byoung Whui; Park, In Won; Chung, Man Pyo; Shin, Hyoung Doo; Song, Jin Woo; Kim, Dong Soon; Park, Choon-Sik; Shim, Young-Soo
Issue Date
BioMed Central
Respiratory Research, 12(1):73
Interleukin-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.

One 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.

The 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).

The 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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