The association of Toll-like receptor 4 gene polymorphisms with the development of emphysema in Japanese subjects: a case control study
| Autor: | Yunden Droma, Nobumitsu Kobayashi, Masayuki Hanaoka, Yoshihiko Katsuyama, Masao Ota, Keishi Kubo, Michiko Ito, Masanori Yasuo, Yoshiaki Kitaguchi, Kayoko Ikegawa, Toshimichi Horiuchi |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Genotype lcsh:Medicine Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Linkage Disequilibrium General Biochemistry Genetics and Molecular Biology Pulmonary Disease Chronic Obstructive Asian People Gene Frequency Forced Expiratory Volume Odds Ratio medicine Humans Genetic Predisposition to Disease Allele lcsh:Science (General) Allele frequency lcsh:QH301-705.5 Alleles Aged Emphysema Medicine(all) COPD Biochemistry Genetics and Molecular Biology(all) Haplotype lcsh:R Case-control study General Medicine Odds ratio Middle Aged medicine.disease Up-Regulation respiratory tract diseases Toll-Like Receptor 4 Phenotype Haplotypes lcsh:Biology (General) Case-Control Studies Immunology Female Research Article lcsh:Q1-390 |
| Zdroj: | BMC Research Notes, Vol 5, Iss 1, p 36 (2012) BMC Research Notes |
| ISSN: | 1756-0500 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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