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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BMC
2011-06-01
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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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