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

<p>Abstract</p> <p>Background</p> <p>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 evaluat...

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Main Authors: Chung Man, Park In, Choi Byoung, Park Jeong, Jeong Sung, Lee Kye, Jung Ki-Suck, Han Sung, Kim Young, Kim Yang-Ki, Uh Soo-Taek, Shin Hwa-Kyun, Park Jai-Soung, Jang An-Soo, Kim Do-Jin, Park Jong-Sook, Park Sung-Woo, Lee Shin-Hwa, Park Byung-Lae, Ahn Mi-Hyun, Shin Hyoung, Song Jin, Kim Dong, Park Choon-Sik, Shim Young-Soo
Format: Article
Language:English
Published: BMC 2011-06-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/12/1/73
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author Chung Man
Park In
Choi Byoung
Park Jeong
Jeong Sung
Lee Kye
Jung Ki-Suck
Han Sung
Kim Young
Kim Yang-Ki
Uh Soo-Taek
Shin Hwa-Kyun
Park Jai-Soung
Jang An-Soo
Kim Do-Jin
Park Jong-Sook
Park Sung-Woo
Lee Shin-Hwa
Park Byung-Lae
Ahn Mi-Hyun
Shin Hyoung
Song Jin
Kim Dong
Park Choon-Sik
Shim Young-Soo
author_facet Chung Man
Park In
Choi Byoung
Park Jeong
Jeong Sung
Lee Kye
Jung Ki-Suck
Han Sung
Kim Young
Kim Yang-Ki
Uh Soo-Taek
Shin Hwa-Kyun
Park Jai-Soung
Jang An-Soo
Kim Do-Jin
Park Jong-Sook
Park Sung-Woo
Lee Shin-Hwa
Park Byung-Lae
Ahn Mi-Hyun
Shin Hyoung
Song Jin
Kim Dong
Park Choon-Sik
Shim Young-Soo
author_sort Chung Man
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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, <it>p </it>= 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 (<it>p </it>= 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 (<it>p </it>= 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (<it>p </it>= 0.002).</p> <p>Conclusion</p> <p>The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.</p>
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spelling doaj.art-af0b6438ad2d4c23bf192e2b273df0372022-12-21T23:15:21ZengBMCRespiratory Research1465-99212011-06-011217310.1186/1465-9921-12-73A 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 modeChung ManPark InChoi ByoungPark JeongJeong SungLee KyeJung Ki-SuckHan SungKim YoungKim Yang-KiUh Soo-TaekShin Hwa-KyunPark Jai-SoungJang An-SooKim Do-JinPark Jong-SookPark Sung-WooLee Shin-HwaPark Byung-LaeAhn Mi-HyunShin HyoungSong JinKim DongPark Choon-SikShim Young-Soo<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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, <it>p </it>= 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 (<it>p </it>= 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 (<it>p </it>= 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (<it>p </it>= 0.002).</p> <p>Conclusion</p> <p>The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.</p>http://respiratory-research.com/content/12/1/73
spellingShingle Chung Man
Park In
Choi Byoung
Park Jeong
Jeong Sung
Lee Kye
Jung Ki-Suck
Han Sung
Kim Young
Kim Yang-Ki
Uh Soo-Taek
Shin Hwa-Kyun
Park Jai-Soung
Jang An-Soo
Kim Do-Jin
Park Jong-Sook
Park Sung-Woo
Lee Shin-Hwa
Park Byung-Lae
Ahn Mi-Hyun
Shin Hyoung
Song Jin
Kim Dong
Park Choon-Sik
Shim Young-Soo
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
Respiratory Research
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://respiratory-research.com/content/12/1/73
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