The association of Toll-like receptor 4 gene polymorphisms with the development of emphysema in Japanese subjects: a case control study View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-12

AUTHORS

Michiko Ito, Masayuki Hanaoka, Yunden Droma, Nobumitsu Kobayashi, Masanori Yasuo, Yoshiaki Kitaguchi, Toshimichi Horiuchi, Kayoko Ikegawa, Yoshihiko Katsuyama, Keishi Kubo, Masao Ota

ABSTRACT

BACKGROUND: The principal role of Toll-like receptor 4 (TLR4) is the induction of immune responses to lipopolysaccharides. Previously, mice deficient in the TLR4 gene exhibited up-regulation of the NADPH oxidase system in the lungs. This resulted in increased oxidant generation and elastolytic activity, which led to pulmonary emphysema. It was suggested that TLR4 might maintain constitutive lung integrity by modulating oxidant generation. We investigated whether single nucleotide polymorphisms (SNPs) in the TLR4 gene were associated with the emphysema phenotype in Japanese subjects with chronic obstructive pulmonary disease (COPD). RESULTS: Seven SNPs in the TLR4 gene (rs10759930, rs1927914, rs12377632, rs2149356, rs11536889, rs7037117, and rs7045953) were genotyped with allelic discrimination assays. The frequencies of SNPs were compared between 106 patients with the emphysema phenotype of COPD and 137 healthy smokers. We found that the positivity of the individuals with the major G allele of rs11536889 was significantly less in the emphysema group than the control group (p = 0.019). The frequencies of the minor C allele and the distribution of the CC genotype as well as the frequency of the major haplotype that carried the minor C allele of rs11536889 were all significantly higher in the emphysema group than the control group (p = 0.0083, 0.019, and 0.004, respectively). Furthermore, the strength of the association of the CC genotype with the emphysema phenotype was in an odds ratio of 2.60 with 95% confidence intervals from 1.17 to 5.78. However, these significances were not apparent after adjust for age and smoking history by logistic regression. No associations were observed between the rs11536889 and the low attenuation area score, the forced expiratory volume, and the carbon monoxide diffusion capacity in the emphysema group. CONCLUSIONS: The minor C allele of the rs11536889 SNP in the TLR4 gene is likely associated with the risk of developing emphysema in the Japanese population. More... »

PAGES

36

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1756-0500-5-36

DOI

http://dx.doi.org/10.1186/1756-0500-5-36

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044563429

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22251849


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