NLRP3 rs1539019 is significantly associated with chronic obstructive pulmonary disease in a Chinese Han population: a case-control study.

OBJECTIVE: COPD is a complex respiratory disease characterized by chronic airway inflammation and the airflow limitations are not fully reversible due to the combination of genetic and environmental factors. Genetic factors such as polymorphisms, may affect the susceptibility of COPD. In the present study, we examined the association between the polymorphisms of three genes and COPD risk in a Chinese Han population. PATIENTS AND METHODS: A total of 375 COPD patients and 284 control subjects were recruited from November 2018 to June 2021. Data on demographic basic information, smoking status, history of coal dust exposure, and peripheral blood were collected from subjects of two groups. Three polymorphisms (NLRP3 rs1539019, LAMB1 rs4320486,  IL-6 rs1800796) were analyzed. Logistic analysis was used to evaluate the genetic contribution of selected SNPs to COPD susceptibility. RESULTS: The AC genotype of NLRP3 rs1539019 significantly decreased COPD risk compared with CC genotype (adjusted OR = 0.508, 95% CI 0.336-0.767). In the stratification analyses, the AC genotype significantly decreased the risk of COPD in subjects aged 60 and over (p=0.005; adjusted OR = 0.553; 95% CI 0.366-0.835) with current smoking status (p=0.002; adjusted OR = 0.419; 95% CI 0.240-0.732) when compared with AA+CC genotype. Moreover, a significantly decreased risk for GOLD III COPD was found in genotype AC of NLRP3 rs1539019 (p=0.006; adjusted OR = 0.502; 95% CI 0.306-0.822). CONCLUSIONS: Our present study revealed that the genotype AC of NLRP3 rs1539019 is related to a decreased risk of COPD in a Chinese Han population, a large-sample, multi-center, multi-ethnic study is needed to further confirm our study.

Heterozygous Ins/Del genotype of the CASP8 rs3834129 polymorphism significantly decreases the risk of coal workers' pneumoconiosis in a Chinese Han population: a case-control study.

OBJECTIVE: Coal workers' pneumoconiosis (CWP) is a chronic inflammatory and fibrotic pulmonary disease that involves a complex interaction of multiple environmental and genetic factors. Polymorphism, as a genetic factor, may affect the onset of the disease in susceptible populations. The present study investigated the association between the polymorphisms of six genes and CWP risk in a Chinese Han population. PATIENTS AND METHODS: Six polymorphisms (CASP8 rs3834129, IL1A rs1800587, IL6 rs1800796, IL4 rs2070874, TNFA rs361525, and NLRP3 rs1539019) were examined in 222 CWP subjects and 247 dust-exposed control subjects. RESULTS: The CASP8 rs3834129 Ins/Del genotype significantly decreased CWP risk (p=0.040; adjusted odds ratio [OR] = 0.586; 95% confidence interval [CI] 0.367-0.935) compared with the Ins/Ins genotype. Stratification analyses revealed a significant interaction between the heterozygous Ins/Del genotype and age. Compared with the Ins/Ins + Del/Del genotype, this was particularly evident among subjects aged 41-60 (p<0.001; adjusted OR = 0.054; 95% CI 0.007-0.420) and those with an exposure time of 20-29 years (p=0.014; adjusted OR = 0.392; 95% CI 0.183-0.842). This decreased risk was also found in the group with former smokers (p=0.012; adjusted OR = 0.448; 95% CI 0.238-0.844). Findings revealed that the heterozygous Ins/Del genotype of CASP8 rs3834129 was related to a significantly decreased risk of stage I CWP (p=0.045; adjusted OR = 0.592; 95% CI 0.353-0.992), but not stage II or III CWP. CONCLUSIONS: Our study indicated that the heterozygous Ins/Del genotype of CASP8 rs3834129 significantly decreased CWP risk in a Chinese Han population.

Adiponectin inhibits oxidative stress in human prostate carcinoma cells.

BACKGROUND: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC), but the mechanisms underlying this relationship remain to be fully elucidated. Oxidative stress (OS) is a key process in the development and progression of PC. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy humans, but at reduced levels in obese subjects. Moreover, case-control studies also document lower levels of serum adiponectin in PC patients compared with healthy individuals. METHODS: Human 22Rv1 and DU-145 PC cell lines were examined for the generation of OS and detoxification of reactive oxygen species after treatment with adiponectin. Normality was confirmed using the Shapiro-Wilk test and results were analyzed using a one-way analysis of variance. RESULTS: We demonstrate that adiponectin increased cellular anti-oxidative defense mechanisms and inhibited OS in a significant and dose-dependent manner. We show that adiponectin treatment decreased the generation of superoxide anion in both cell lines, whereas the transcript levels of NADPH oxidase (NOX)2 and NOX4 increased. We also found indications of an overall anti-oxidative effect, as the total anti-oxidative potential, catalase activity and protein levels, and manganese superoxide dismutase protein levels increased significantly (P<0.05) in both cell lines after treatment with adiponectin. CONCLUSION: Lower levels of adiponectin in obese individuals may result in higher levels of prostatic OS, which may explain the clinical association between obesity, hypoadiponectinemia and PC.

Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase.

Androgen deprivation therapy (ADT) facilitates the response of prostate cancer (PC) to radiation. Androgens have been shown to induce elevated basal levels of reactive oxygen species (ROS) in PC, leading to adaptation to radiation-induced cytotoxic oxidative stress. Here, we show that androgens increase the expression of p22(phox) and gp91(phox) subunits of NADPH oxidase (NOX) and ROS production by NOX2 and NOX4 in PC. Pre-radiation treatment of 22Rv1 human PC cells with NOX inhibitors sensitize the cells to radiation similarly to ADT, suggesting that their future usage may spare the need for adjuvant ADT in PC patients undergoing radiation.