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

<p>Abstract</p> <p>Background</p> <p>The principal role of Toll-like receptor 4 (TLR4) is the induction of immune responses to lipopolysaccharides. Previously, mice deficient in the <it>TLR4 </it>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 <it>TLR4 </it>gene were associated with the emphysema phenotype in Japanese subjects with chronic obstructive pulmonary disease (COPD).</p> <p>Results</p> <p>Seven SNPs in the <it>TLR4 </it>gene (<it>rs10759930</it>, <it>rs1927914</it>, <it>rs12377632</it>, <it>rs2149356, rs11536889</it>, <it>rs7037117</it>, and <it>rs7045953</it>) 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 <it>rs11536889 </it>was significantly less in the emphysema group than the control group (<it>p </it>= 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 <it>rs11536889 </it>were all significantly higher in the emphysema group than the control group (<it>p </it>= 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 <it>rs11536889 </it>and the low attenuation area score, the forced expiratory volume, and the carbon monoxide diffusion capacity in the emphysema group.</p> <p>Conclusions</p> <p>The minor C allele of the <it>rs11536889 </it>SNP in the <it>TLR4 </it>gene is likely associated with the risk of developing emphysema in the Japanese population.</p

山地源頭部森林流域における地下水・渓流水の動態に関する水文化学的研究

京都大学0048新制・課程博士博士(農学)甲第9653号農博第1281号新制||農||848(附属図書館)学位論文||H14||N3685(農学部図書室)UT51-2002-G411京都大学大学院農学研究科地域環境科学専攻(主査)教授 谷 誠, 教授 三野 徹, 教授 水山 高久学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDFA

Hydrologic effects on methane dynamics in riparian wetlands in a temperate forest catchment

To understand how hydrological processes affect biogeochemical and methane (CH_4) cycles in temperate riparian wetlands, we measured CH_4 fluxes and dissolved chemical constituents and CH_4 concentrations in groundwater, and monitored several environmental factors in wetlands located within a forested headwater catchment in a warm, humid climate in Japan. Variation in redox components dissolved in groundwater, including nitrate (NO_3￣), Mn, Fe, and sulfate (SO_42￣), depended on temperature and soil-water conditions. Strongly reducing conditions usually occurred in the high-temperature months of July, August, and September. Dissolved CH_4 in groundwater changed with redox conditions and was highest in summer and lowest in winter. CH_4 emissions from riparian wetlands were observed almost throughout the year and displayed clear seasonality. Occasionally in summer, emission rates were more than 4 orders of magnitude greater than hillslope uptake rates. Although CH_4 emissions increased markedly during most of the summer, they were constrained by (1) fluctuation of the water table, which when lowered can shift the subsurface zone to a more oxidized condition, and (2) the oxygen-rich water such as precipitation and lateral subsurface flow from the hillslope. These results suggest that hydrological processes in forest headwater catchments play an important role in supplying oxygen to soils and consequently affect biogeochemical cycles, including CH_4 formation, and that small wetlands in forest watersheds function as large sources of CH_4, especially in regions with warm humid summers