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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.
authors.affiliation: Div of Allergy and Respiratory Medicine, Dept of Internal Medicine, Soonchunhyang Univ, Bucheon Hospital, 1174 Jung-dong, Wonmi-gu, Bucheon 420-020, Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Ahn
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Shin-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Do-Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: An-Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Jai-Soung
authors.initials: JS
authors.lastname: Park
authors.forename: Hwa-Kyun
authors.initials: HK
authors.lastname: Shin
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yang-Ki
authors.initials: YK
authors.lastname: Kim
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Han
authors.forename: Ki-Suck
authors.initials: KS
authors.lastname: Jung
authors.forename: Kye Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Jeong
authors.forename: Jeong Woong
authors.initials: JW
authors.lastname: Park
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: In Won
authors.initials: IW
authors.lastname: Park
authors.forename: Man Pyo
authors.initials: MP
authors.lastname: Chung
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Song
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Kim
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Shim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006720:Homozygote; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8