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In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11-8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction.

Oxidative stress and inflammation play a key role in the age-related decline in the respiratory function. Adipokine in relation to the metabolic and inflammatory systems is attracting growing interest in the field of respiratory dysfunction. The present clinical and experimental studies investigated the role of the disulfide bond-forming oxidoreductase A-like protein ( DsbA-L ) gene, which has antioxidant and adiponectin multimeric (i.e. activation) properties, on the respiratory function of the elderly. We performed a retrospective longitudinal genotype-phenotype relationship analysis of 318 Japanese relatively elderly participants (mean age ± standard deviation: 67.0 ± 5.8 years) during a health screening program and an in vitro DsbA-L knock-down evaluation using 16HBE14o-cells, a commonly evaluated human airway epithelial cell line. The DsbA-L rs1917760 polymorphism was associated with a reduction in the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and %FEV1 and with the elevation of the prevalence of FEV1/FVC < 70%. We also confirmed that the polymorphism was associated with a decreased respiratory function in relation to a decrease in the ratio of high-molecular-weight adiponectin/total adiponectin (as a marker of adiponectin multimerization) and an increase in the oxidized human serum albumin (as an oxidative stress marker). Furthermore, we clarified that DsbA-L knock-down induced oxidative stress and up-regulated the mucus production in human airway epithelial cells. These findings suggest that the DsbA-L gene may play a role in protecting the respiratory function of the elderly, possibly via increased systemic adiponectin functions secreted from adipocytes or through systemic and/or local pulmonary antioxidant properties.

The patatin-like phospholipase domain containing protein 3 ( ) rs738409 polymorphism (c.444C>G) is the most well-known genetic risk factor for non-alcoholic fatty liver disease (NAFLD), but whether or not physical activity influences the association between the genotype and risk of NAFLD is unclear. A retrospective longitudinal analysis was conducted among 352 Japanese subjects. Each type of physical activity was assigned a metabolic equivalent (MET), and the subjects were classified into sedentary, low or high groups using the \"METS*T\" (METs × hours per week) value of 5 or 21 as a threshold. Among the G/G genotype carriers, the high and low METS*T groups had a lower risk of NAFLD than the sedentary METS*T group (odds ratio [95% confidence interval]: 0.14 [0.02-0.99] and 0.16 [0.03-1.04], respectively). Furthermore, the C/C or C/G genotype carriers showed no significant difference in the risk of NAFLD among the three METS*T groups. The rs738409 genotype may be associated with the beneficial effects of physical activity on the risk of NAFLD among elderly Japanese individuals. Further comprehensive investigations are therefore needed to verify the preliminary results.

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females.

Objectives Chronic kidney disease (CKD) is a major public health problem. Epidemiological studies of the relationship between alcohol intake and CKD are scarce in Japan. This cross-sectional study aims to investigate the relationship between frequency of drinking alcohol and CKD in Japanese men. Methods The subjects were 9,196 men (mean ± standard deviation age, 57.9 ± 5.1 years) who underwent a health check-up. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2 . Frequency of alcohol drinking was obtained from questionnaire and divided into five categories: nondrinkers, once or twice a week, three or four times a week, five or six times a week, and everyday drinkers. Results Multivariable-adjusted [age, body mass index, hypertension, diabetes, hyper-low-density lipoprotein (LDL) cholesterolemia, smoking, and physical activity] odds ratios and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Compared with the results for the nondrinkers, the multivariable-adjusted odds ratios of CKD were as follows: 0.76 (95% CI 0.60–0.95) for 1–2 drinks per week, 0.74 (95% CI 0.59–0.93) for 3–4 drinks per week, 0.79 (95% CI 0.64–0.97) for 5–6 drinks per week, and 0.60 (95% CI 0.51–0.71) for everyday drinkers. There was a significant inverse trend across increasing frequency of drinking alcohol ( p  = 0.001 for trend). Conclusions An inverse association was found between frequency of drinking alcohol and CKD in apparently healthy men.

Although height (H) has been considered the principal anthropometric variable governing lung function, the age-dependent differences in its influences on determining spirometric parameters (SPs) have not been conclusively investigated. Moreover, there has been no study centered on age-dependent effects of other anthropometric variables, including body weight (BW) and body fat mass (BFM) on SPs. In addition, the age-dependent influences of these anthropometric variables are anticipated to differ quantitatively between male and female participants. A total of 16,919 nonsmoking healthy Japanese adults (men: 6,116, women: 10,803) were partitioned into six groups stratified by gender and age at intervals of 20-years: young-, middle-, and advanced-age groups of either gender. Using a model in which a SP was described by a logarithmic additive function of age, H, BW, and BFM, we determined the partial regression coefficients of the respective anthropometric variables to predict the reference means of SPs, including FVC, FEV1, FEV1/FVC, PEF, FEF50, and FEF75, in the six groups. Although the impact of H on FVC and FEV1 was relatively homogeneous irrespective of gender and age, its homogeneity faded for flow parameters, particularly in the female middle- and advanced-age groups, indicating that the age-dependent contribution of H to SPs was enhanced more in women. The impact of BW on SPs differed depending on age, and this effect was also more conspicuous for female participants. H and BW generally exerted positive effects on SPs, whereas BFM had negative effects. Opposite effects of BW and BFM were observed in the female middle-age group in particular. The effects of anthropometric variables on spirometric parameters are highly age-dependent, particularly in women, leading to the conclusion that the assumption of age-independent, constant partial regression coefficients of anthropometric variables while predicting the reference mean of a certain spirometric parameter may result in substantial errors.

Objectives The present study aimed to investigate the relationship between airflow limitation (AL) severity and comorbidities in comprehensive health examination. Methods This cross-sectional study included 6661 men and 6044 women aged 40–89 who underwent a lung function test during medical checkups. AL was defined as forced expiratory volume in 1 s/forced vital capacity of < 0.7. Logistic regression analysis was used to assess the association between AL severity and the presence of comorbidities. Results When compared with the normal lung function group, subjects with AL had a higher prevalence of lung cancer (odd ratio (OR) 9.88, 95% confidence interval (CI) 3.88–25.14) in men, hypertension (OR 1.63, 95% CI 1.26–2.10) in women, diabetes and hyperglycemia (OR 1.23, 95% CI 1.02–1.49 in men, OR 1.61, 95% CI 1.18–2.20 in women) in men and women after adjusting for potential confounders. In men, lung cancer and MetS (the Joint Interim Statement: JIS) were significantly associated with moderate-to-very severe AL after adjustment. In women, hypertension, diabetes and hyperglycemia, MetS (JIS), and MetS (the Japanese Committee of the Criteria for MetS: JCCMS) were significantly associated with mild AL after adjustment. Hypertension was significantly associated with moderate-to-very severe AL after adjustment in women. Conclusions Significant relationships were found between AL severity and the presence of comorbid lung cancer in men, hypertension in women, diabetes and hyperglycemia, and MetS in men and women. Knowledge of comorbidities associated with AL should be widely publicized to raise the awareness of chronic obstructive pulmonary disease (COPD).

The aim of this study was to reveal the association between airflow limitation (AL) severity and reduction with work productivity as well as use of sick leave among Japanese workers. This cross-sectional study included 1,378 workers who underwent a lung function test during a health checkup at the Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in 1 second/forced vital capacity of <0.7. Workers completed a questionnaire on productivity loss at work and sick leave. The quality and quantity of productivity loss at work were measured on a ten-point scale indicating how much work was actually performed on the previous workday. Participants were asked how many days in the past 12 months they were unable to work because of health problems. Logistic regression analysis was used to assess the associations between AL severity and the quality and quantity of productivity loss at work as well as use of sick leave. Compared with workers without AL, workers with moderate-to-severe AL showed a significant productivity loss (quality: odds ratio [OR] =2.04, 95% confidence interval [CI]: 1.12-3.71, P=0.02 and quantity: OR =2.19, 95% CI: 1.20-4.00, P=0.011) and use of sick leave (OR =2.69, 95% CI: 1.33-5.44, P=0.006) after adjusting for sex, age, body mass index, smoking status, hypertension, hyperglycemia, dyslipidemia, sleep duration, work hours per day, and workplace smoking environment. AL severity was significantly associated with work productivity loss and use of sick leave. Our findings suggested that early intervention in the subjects with AL at the workforce might be beneficial for promoting work ability.

Objectives There is some evidence that chronic obstructive pulmonary disease and chronic kidney disease (CKD) may be related, perhaps through systemic inflammation, which is common to both. However, this relationship has not yet been clearly demonstrated. The aim of this study was to investigate the association between airflow obstruction, CKD, and C-reactive protein (CRP) levels in Japanese men. Methods The study included 11,587 men, aged 40–88 years, who underwent a health check-up. Airflow obstruction was defined as a forced expiratory volume in 1 s/forced vital capacity of <70%, and its severity was based on the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD). CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m 2 . Results Airflow obstruction was present in 7.9% of the participants, and 10.6% of the participants had CKD. The average CRP levels were 0.11 ± 0.36, 0.13 ± 0.41, and 0.18 ± 0.41 mg/L for subjects with normal lung function, GOLD stage I, and GOLD stage II–IV, respectively. With regard to CKD, the average CRP levels were 0.11 ± 0.32 and 0.18 ± 0.6 mg/L for subjects without and with CKD, respectively. Analysis of covariance showed no significant differences between the CRP level and lung function status or CKD after age was adjusted for. Logistic regression analysis showed no association among subjects with the three different lung function statuses after age, body mass index, hypertension, diabetes, hyper-low-density-lipoprotein-cholesterolemia, smoking, physical activity, and alcohol intake were controlled for. Conclusions Based on the results of this study, we conclude that there is no interrelationship between CRP level, airflow obstruction, and CKD.