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- Title
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.
- Authors
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
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.
- Subjects
SINGLE nucleotide polymorphisms; INTERLEUKIN-8; IDIOPATHIC pulmonary fibrosis; NEUTROPHILS; MESSENGER RNA; GENE expression; LUCIFERASES
- Publication
Respiratory Research, 2011, Vol 12, Issue 6, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/1465-9921-12-73