Association of MC4R (rs17782313) with diabetes and cardiovascular disease in Korean men and women.

BACKGROUND: Diabetes is mostly assessed by the fasting glucose level. Several studies reported that serum fasting glucose levels and cardiovascular disease are associated with MC4R. METHODS: A total of 4294 subjects participated in this study. There were 1810 subjects with cardiovascular disease among the 4294 subjects. We used multivariate linear regression models and multiple logistic regression analysis. RESULTS: Individuals with the TC/CC genotype had a 1.29-fold higher risk of diabetes than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.29; 95% CI, 1.04-1.60). For healthy subjects, the association was significant in women (OR, 1.99; 95% CI, 1.01-3.93). Men with the TC/CC genotype had a 1.21-fold higher risk of cardiovascular disease than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.21; 95% CI, 1.04-1.41). The relationship between MC4R and cardiovascular disease was stronger in lean men (OR, 1.40; 95% CI, 1.12-1.74, p = 0.0028) than in overweight men. CONCLUSIONS: This study suggests that the rs17782313 SNP in MC4R is related to diabetes and the SNP is also associated with cardiovascular disease in lean men.

Effects of Obesity and Family History of Diabetes on the Association of CETP rs6499861 with HDL-C Level in Korean Populations.

OBJECTIVES: The aim of this study was to examine the associations of cholesterol ester transfer protein (CETP) rs6499861 and rs12708980 with high-density lipoprotein cholesterol (HDL-C) considering obesity and family history of diabetes (FHD) in Korean men and women. METHODS: We analyzed the association of CETP single nucleotide polymorphisms (SNPs) with HDL-C among individuals selected from a hospital (n=4 294) and the Bundang-gu area in Korea (n=2 304). RESULTS: We found that the CETP SNP rs6499861 was associated with a lower HDL-C level (effect per allele: -2.044 mg/dL, p<0.0001). Individuals with a rs6499861 CG/GG genotype had a 1.45-fold higher risk of an abnormal level of HDL-C (<40 mg/dL) than those with a CC genotype. This genotype-HDL-C association was stronger in women (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.39-2.85) compared with men (OR, 1.33; 95% CI, 1.10-1.61) and in women with a FHD (OR, 4.82; 95% CI, 1.86-12.5; p=0.0012) compared with women without a family history. Relative to individuals with a CC genotype and body mass index (BMI) <25.69 kg/m2, individuals with a CG/GG genotype and BMI ≥25.69 kg/m2 had an OR (95% CI) of 2.61 (1.97-3.47). CONCLUSIONS: These findings indicate that CETP variants are linked to HDL-C level in Koreans and that this link is stronger in obese men and in women who have a FHD.

Relationship between binge drinking experience and suicide attempts in Korean adolescents: based on the 2013 Korean Youth Risk Behavior Web-based Survey.

OBJECTIVES: Suicide and drinking problems in adolescents are increasing every year, and it is known that suicide is related to drinking. This study aims to identify the relationship between binge drinking experience (BDE) and suicide attempts in Korean adolescents. METHODS: The Ninth Korean Youth Risk Behavior Web-based Survey (KYRBS), conducted in 2013, was used for analysis. Multiple logistic regression analysis was used to identify the relationship between BDE and suicide attempts, and the relationship between BDE and suicide attempts in middle and high school students was stratified by age. RESULTS: BDE and suicide attempts were highly related. The odds ratio (OR) of attempted suicide in BDE was 1.63 times (95% confidence interval [CI], 1.28 to 2.09) higher then non-drinking in males. And the OR of attempted suicide in females was 1.21 times (95% CI, 1.07 to 1.37) higher then non-drinking in non-BDE, 1.79 times (95% CI, 1.47 to 2.19) higher in BDE. BDE was associated with suicide attempts in males aged 12 or 13 years (OR, 3.97; 95% CI, 1.57 to 10.03) and in females aged 15 years (OR, 2.66; 95% CI, 1.79 to 3.96). CONCLUSIONS: BDE is an important factor related to suicide attempts in adolescents. In order to reduce suicide attempts, it is necessary to educate the youth about the regulation of BDE and drinking prevention.

Thymus and activation-regulated chemokine (TARC)/CCL17 and IgE are associated with elderly asthmatics.

BACKGROUND: The pathogenesis of asthma, which is an allergic lung disease, is associated with a variety of allergens such as house dust mite, pollen, and mould, IgE containing serum IgE and allergen-specific-IgE, and inflammatory cytokines including thymus and activation-regulated chemokine (TARC)/CCL17. Because aging is an essential factor in the pathogenesis of asthma, we examined biomarkers related to asthmatic subjects depending on age. RESULTS: Physiological indices such as FEV1(forced expiratory capacity in 1 s), FEV1 (% predicted), and FEV1/FVC(forced vital capacity) (%) in asthmatic subjects were lower than those in normal subjects. Total IgE, Der p1 specific IgE, and Der f1 specific IgE were elevated in serum of asthmatics relative to normal individuals. Regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5 in serum and interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein (MCP)-1/CCL2, RANTES, and macrophage inflammatory protein (MIP)-1α/CCL3 in bronchoalveolar lavage fluid (BALF) of asthmatic subjects were higher than in normal individuals. Upon classification of experimental groups depending on age, physiological indices and Der p1-specific IgE (class) were decreased in middle aged adult and elderly adult groups relative to the young adult group. TARC levels in serum were strongly elevated in the elderly adult group relative to the young adult and the middle aged adult groups. TARC in serum was related to total IgE in serum in the elderly adult group. CONCLUSIONS: Taken together, although TARC in serum and BALF is not different between normal and asthmatic individuals, TARC increases in serum of elderly asthmatic subjects. The level of TARC has a positive effect on the level of IgE in the elderly adult group. These findings may help us better understand the relationship of pathogenesis of allergic diseases and aging.

Effect of smoking on the association of HHEX (rs5015480) with diabetes among Korean women and heavy smoking men.

BACKGROUND: Several genome-wide association studies (GWAS) for serum fasting glucose levels have reported HHEX as possibly causal. The objective of this study was to examine the joint effect of smoking on the association of diabetes with the HHEX rs5015480 polymorphism among Korean subjects. METHODS: This replication study included a total of 4240 individuals, and multivariate linear regression and multiple logistic regression models were used. We examined the combined effect of smoking on the relationship between HHEX rs5015480 and diabetes. RESULTS: The rs5015480 SNP in the HHEX gene was related to the mean FBS level (effect per allele, 1.572 mg/dL, p = 0.0122). Females with the CC genotype had a 2.68 times higher (range, 1.05-6.82 times) risk of diabetes than those with the TT/TC genotype. Although the association was stronger in female subjects (OR, 4.46; 95% CI, 1.15-17.3, p = 0.0304) among healthy individuals (N = 2461), the association between HHEX and diabetes was much stronger in male heavy smokers (OR, 4.03; 95% CI, 1.19-13.6, p = 0.0247) than in nonsmokers (p = 0.9709) and ex-smokers (p = 0.2399). The interaction of smoking was also statistically significant (P for interaction =0.0182). CONCLUSIONS: This study clearly demonstrates that a genetic variant in HHEX influences fasting glucose levels in Korean women and male heavy smokers.

Association between smoking and gout: a meta-analysis.

Previous studies showed that smoking is linked with the decreased risk of gout, but the results remain controversial. The aim of this meta-analysis was to determine the associations between smoking and the risk of gout. A systematic literature search of PubMed and EMBASE was conducted. Data were extracted by two independent reviewers. The pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of associations, using random effects and fixed effects models. Five studies with a total of 17,915,507 participants with 16,880 gouts were enrolled. Heterogeneity among the effect sizes of five studies was reported as I2 = 87.9%. Our meta-analysis indicated that smoking (ever- vs non-, OR = 0.87, 95% CI = 0.67-1.12) was not associated with the risk of gout in random effects model, whereas there was an association between smoking (ever- vs non-, OR = 0.70, 95% CI = 0.65-0.74) and gout risk in fixed effects model. Our finding indicates that smoking may not be involved in the risk of gout. However, further studies are still needed to confirm our results.

Detrimental Effects of Higher Body Mass Index and Smoking Habits on Menstrual Cycles in Korean Women.

BACKGROUND: Alteration of menstrual cycle by individual lifestyles and unfavorable habits may cause menstrual irregularity. We aimed to investigate the relationship between lifestyle factors and menstrual irregularity in Korean women using data from the Fifth Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012. MATERIALS AND METHODS: This cross-sectional study included 3779 nondiabetic Korean women aged 19-49 years who did not take any oral contraceptives or sex hormonal compounds. We examined the association of menstrual irregularity with age, body mass index (BMI), drinking experience, and smoking habits. RESULTS: Age, Asian BMI, marriage status, age at menarche, and smoking habits were significantly associated with menstrual cycle irregularity (p < 0.01). The prevalence of menstrual irregularity was significantly increased at younger ages: 18.4%, 10.3%, and 10.5% at 19-29, 30-39, and 40-49 years, respectively. Moreover, obesity groups, defined as per Asian BMI using modified WHO criteria, were strongly associated with menstrual irregularity. BMI 25.0-29.9 [obesity class I] (adjusted odds ratios [OR], 1.94; 95% confidence intervals [CI], 1.37-2.74) and ≥30.0 [obesity class II] (adjusted OR, 2.18; 95% CI, 1.22-3.91) presented significantly higher risk of menstrual irregularity compared with BMI 18.5-22.9 [normal weight]. Multivariable analysis revealed that high BMI in younger women aged 19-29 years (p < 0.001) and smoking habits in middle-aged women aged 30-39 years (p < 0.005) significantly predicted menstrual irregularity. CONCLUSION: This study substantiated that menstrual irregularity was closely associated with higher BMI and smoking habits in nondiabetic Korean women. Weight loss and smoking cessation should be recommended to promote women's reproductive health.

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

AIM: To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS: The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. RESULTS: Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION: This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.

Usual alcohol consumption and suicide mortality among the Korean elderly in rural communities: Kangwha Cohort Study.

BACKGROUND: The evidence from prospective studies on whether greater usual alcohol consumption is associated with a higher risk of death by suicide in the general population is inconclusive. METHODS: 6163 participants (2635 men; 3528 women) in a 1985 survey among rural residents in Korea aged 55 years and above were followed until 2008. A Cox model was used to calculate HRs of suicide death after adjustment for demographic, socioeconomic and health-related confounders. RESULTS: 37 men and 24 women died by suicide. Elderly persons who consumed alcohol daily, 70 g alcohol (5 drinks) or more per drinking day, or 210 g alcohol (15 drinks) or more per week had higher suicide mortality (p<0.05), compared with non-drinkers. An increase of one drinking day per week (HR=1.17, 95% CI 1.05 to 1.31), 70 g (5 drinks) additional alcohol intake per drinking day (HR=1.38, 95% CI 1.13 to 1.70), and 140 g (10 drinks) additional alcohol intake per week was associated with a 17%, 38% and 12% higher risk of suicide death, respectively. Women had a higher relative risk of suicide death associated with alcohol consumption, compared with men. CONCLUSIONS: A greater frequency and amount of usual alcohol consumption was linearly associated with higher suicide death. Given the same amount of alcohol consumption, women might have a higher relative risk of suicide than men. Our findings support 'the lower the better' for alcohol intake, no protective effect of moderate alcohol consumption, and a sex-specific guideline (lower alcohol threshold for women) as actions to prevent suicide death.

Effect of obesity on the association between MYL2 (rs3782889) and high-density lipoprotein cholesterol among Korean men.

High-density lipoprotein (HDL) cholesterol levels are associated with a decreased risk of coronary artery disease. Several genome-wide association studies that have examined HDL cholesterol levels have implicated myosin light chain 2 regulatory cardiac slow (MYL2) as a possible causal factor. Herein, the association between the rs3782889 single-nucleotide polymorphism (SNP) in the MYL2 gene and HDL cholesterol levels was tested in the Korean population. A total of 4294 individuals were included in a replication study with MYL2 SNP rs3782889. SNP rs3782889 in the MYL2 gene was associated with mean HDL cholesterol level (effect per allele, -1.055 mg dl(-1), P=0.0005). Subjects with the CT/CC genotype had a 1.43-fold (range 1.19-1.73-fold) higher risk of an abnormal HDL cholesterol level (<40 mg dl(-1)) than subjects with the TT genotype. When analyzed by sex, the MYL2 association was stronger in men than that in women. When analyzed by body mass index (BMI), the MYL2 association was much stronger in male subjects with BMI ⩾26.44 kg m(-2) (odds ratio (OR)=2.68; 95% confidence interval (CI)=1.87-3.84; P<0.0001) than that in male subjects with BMI <26.44 kg m(-2). When compared with subjects having the TT genotype and BMI <26.44 kg m(-2), ORs (95% CI) were 3.30 (2.41-4.50) in subjects having the CT/CC genotype and BMI ⩾26.44 kg m(-2) (P for interaction <0.0001). Our results clearly demonstrate that genetic variants in MYL2 influence HDL cholesterol levels in Korean obese male subjects.

Body mass index and mortality among Korean elderly in rural communities: Kangwha Cohort Study.

BACKGROUND: The relationship between body mass index (BMI) and mortality may differ by ethnicity, but its exact nature remains unclear among Koreans. The study aim was to prospectively examine the association between BMI and mortality in Korean. METHODS: 6166 residents (2636 men; 3530 women) of rural communities (Kangwha County, Republic of Korea) aged 55 and above were followed up for deaths from 1985-2008. The multivariable-adjusted hazard ratios were calculated using the Cox proportional hazards model. RESULTS: During the 23.8 years of follow-up (an average of 12.5 years in men and 15.7 years in women), 2174 men and 2372 women died. Men with BMI of 21.0-27.4 and women with BMI of 20.0-27.4 had a minimal risk for all-cause mortality. A lower BMI as well as a higher BMI increased the hazard ratio of death. For example, multivariable-adjusted hazard ratios associated with BMI below 16, and with BMI of 27.5 and above, were 2.4 (95% CI = 1.6-3.5) and 1.5 (95% CI = 1.1-1.9) respectively, in men, compared to those with BMI of 23.0-24.9. This reverse J-curve association was maintained among never smokers, and among people with no known chronic diseases. Higher BMI increased vascular mortality, while lower BMI increased deaths from vascular diseases, cancers, and, especially, respiratory diseases. Except for cancers, these associations were generally weaker in women than in men. CONCLUSIONS: A reverse J-curve association between BMI and all-cause mortality may exist. BMI of 21-27.4 (rather than the range suggested by WHO of 18.5-23 for Asians) may be considered a normal range with acceptable risk in Koreans aged 55 and above, and may be used as cut points for interventions. More concern should be given to people with BMI above and below a BMI range with acceptable risk. Further studies are needed to determine ethnicity-specific associations.

Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean population by genome-wide association studies including gene-environment interactions.

Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial disease. Although smoking is a main risk factor for obstructive impairment, not all smokers develop this critical disease. We conducted a genome-wide association study to identify the association between genetic variants and pulmonary function and also examined how these variants relate to lung impairment in accordance with smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319) and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we analyzed the association between genetic variants (single-nucleotide polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using multivariate linear regression models. Similar analyses were conducted after stratification by smoking status. Four genome-wide significant signals in the FAM13A gene (the strongest signal at rs2609264, P=1.76 × 10(-7) in a combined set) were associated with FEV1/FVC. For the association with ratio, the effect size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 × 10(-7)) as compared with the TCAG haplotype (reference haplotype) in a combined set. There was also a significant interaction of FAM13A haplotypes with heavy smoking on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes also interacted with heavy smoking to affect the risk of reduced pulmonary function.

Association between all-cause mortality and insurance status transition among the elderly population in a rural area in Korea: Kangwha Cohort Study.

The study purpose was to examine the association between health insurance transition and all-cause mortality. 3206 residents in Korea who participated in two surveys in 1985 and 1994, were followed-up during 1994-2008. Adjusted hazard ratios (aHR) were calculated using Cox hazard model. Participants were divided into four groups by insurance transition (the "National Health Insurance (NHI)-NHI", "NHI-Medicaid", "Medicaid-NHI", and "Medicaid-Medicaid" groups), where NHI-Medicaid means participants covered by NHI in 1985 but by Medicaid in 1994. For men covered by NHI in 1985, the mortality risk in the NHI-Medicaid was higher (aHR=1.47) than in the NHI-NHI. For men and women, covered by Medicaid in 1985, aHR was non-significantly lower in the Medicaid-NHI than in the Medicaid-Medicaid. When four groups were analyzed together, men in the Medicaid-Medicaid (aHR=1.67) and NHI-Medicaid (aHR=1.46) groups had higher mortality risk than males in the NHI-NHI, whereas no significant difference was observed for females. In conclusion, transition from NHI to Medicaid increases mortality risk, and transition from Medicaid to NHI may mitigate risk, while remaining on Medicaid pose the greatest risk, especially for men. Therefore, policy makers should strengthen coverage for Medicaid. The weak effects of transition from NHI to Medicaid on mortality for women require validation.

The ABCG2 Polymorphism rs2725220 Is Associated with Hyperuricemia in the Korean Population.

Elevated serum uric acid levels are associated with a variety of adverse health outcomes, including gout, hypertension, diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Several genome-wide association studies on uric acid levels have implicated the ATP-binding cassette, subfamily G, member 2 (ABCG2) gene as being possibly causal. We investigated an association between the single-nucleotide polymorphism (SNP) rs2725220 in the ABCG2 gene and uric acid levels in the Korean population. A total of 991 subjects in Seoul City were used for a replication study with ABCG2 SNP rs2725220. The rs2725220 SNP in the ABCG2 gene was associated with mean uric acid levels (effect per allele 0.25 mg/dL, p < 0.0001). Subjects with the GC/CC genotype had a 1.78-fold (range, 1.22- to 2.62-fold) higher risk of having abnormal uric acid levels (≥7.0 mg/dL) than subjects with the GG genotype. When analyzed by gender, the association with ABCG2 was stronger in men than in women. The association with ABCG2 was much stronger in male subjects with body mass index (BMI) ≥ 26.4 (odds ratio, 5.09; 95% confidence interval, 2.41 to 10.8) than in male subjects with BMI < 26.4. This study clearly demonstrates that genetic variations in ABCG2 influence uric acid levels in Korean adults.

Replication of genetic effects of MC4R polymorphisms on body mass index in a Korean population.

Obesity is associated with a variety of adverse health risks. Several genome-wide association studies of obesity have identified candidate genes, including the fat mass and obesity-associated gene (FTO) and the melanocortin-4 receptor (MC4R) gene. We carried out a replication study of MC4R and FTO variants in a Korean cohort. A total of 2,281 subjects in the Bundang-gu region were analyzed using selected markers. Another 8,826 subjects in the Ansung/Ansan city were used for a meta-analysis. Two single nucleotide polymorphisms (SNPs) in FTO and one SNP in the MC4R gene were genotyped. Multivariate linear regression models were employed to test for genotypic effects on obesity traits while adjusting for age and sex using an additive model. The SNP rs17782313 near the MC4R gene was associated with mean body mass index in the Bundang-gu cohort (effect per allele 0.288 kg/m(2), p = 0.0023). The p value for meta-analysis of rs17782313 in all 11,107 individuals in the Bundang-gu and Ansung/Ansan cohorts was 2.82 × 10(-6) (effect per allele 0.22 kg/m(2)). Two SNPs in FTO were significantly associated with weight (effect per allele 0.969 kg, p = 0.011 for rs9939609; 0.943, p = 0.014 for rs8050136) but not with body mass index. This study demonstrates that genetic variants in MC4R influence obesity traits in Korean adults.

Effects of SLC2A9 variants on uric acid levels in a Korean population.

Elevated uric acid levels are associated with a variety of adverse health risks. Genome-wide association studies have identified several candidate genes associated with serum uric acid levels, including SLC2A9. We carried out a replication study of SLC2A9 variants in two Korean cohorts. A total of 961 participants in Seoul City were genotyped using a genome-wide marker panel, and 1,859 participants in the Bundang-Gu area were used for a replication study with a selected marker. Multivariate linear regression models were employed to test for genotypic effects on uric acid levels while adjusting for age, sex, and smoking status using an additive model. The top single nucleotide polymorphism associated with uric acid levels was rs4529048 in the SLC2A9 gene on chromosome 4 (P = 2.12 × 10(-6) in the Seoul City sample; P = 1.55 × 10(-9) in the Bundang-Gu sample). The meta-analysis P value for rs4529048 in the combined 2,820 individuals was 1.17 × 10(-14). This study demonstrates that genetic variants in SLC2A9 influence uric acid levels in Korean adults.

Prediction of Colorectal Cancer Risk Using a Genetic Risk Score: The Korean Cancer Prevention Study-II (KCPS-II).

Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, we developed a prediction model of CRC using genetic risk scores (GRS) and evaluated the effects of conventional risk factors, including family history of CRC, in combination with GRS on the risk of CRC in Koreans. This study included 187 cases (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were calculated with most significantly associated single-nucleotide polymorphism with CRC through a genomewide association study. The area under the curve (AUC) increased by 0.5% to 5.2% when either counted or weighted GRS was added to a prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men and women. Furthermore, the risk of CRC significantly increased for individuals with a family history of CRC in the highest quartile of GRS when compared to subjects without a family history of CRC in the lowest quartile of GRS (counted GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men; OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to 218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest that in Koreans, especially in Korean men, GRS improve the prediction of CRC when considered in conjunction with age and family history of CRC.

Suppressing effect of resveratrol on the migration and invasion of human metastatic lung and cervical cancer cells.

The antioxidant 3,4',5 tri-hydroxystilbene (resveratrol), a phytoalexin found in grapes, shows cancer preventive activities, including inhibition of migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of resveratrol on tumor metastasis, especially in human metastatic lung and cervical cancers is not clear. A non-cytotoxic dosage of resveratrol causes a reduction in the generation of reactive oxygen species, and suppresses phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration in both A549 and HeLa cells. Resveratrol also decreases both the expression and the enzymatic activity of matrix metalloproteinase-9 (MMP-9), and the promoter activity of PMA-stimulated MMP-9 is also inhibited. However, resveratrol does not affect either the expression or the proteolytic activity of MMP-2. Our results also show that resveratrol suppresses the transcription of MMP-9 by the inhibition of both NF-κB and AP-1 transactivation. These results indicate that resveratrol inhibits both NF-κB and AP-1 mediated MMP-9 expression, leading to suppression of migration and invasion of human metastatic lung and cervical cancer cells. Resveratrol has potential for clinical use in preventing invasion by human metastatic lung and cervical cancers.

Life satisfaction and mortality in elderly people: the Kangwha Cohort Study.

BACKGROUND: As well as biomedical risk factors, psychological factors have been reported to be related to mortality rate. The purpose of this study was to examine the relationship between life satisfaction and mortality in elderly people through an 11.8-year follow-up study of a prospective cohort. METHODS: Among 3,600 participants of the Kangwha Cohort Study who survived in 1994, 1,939 respondents of the Life Satisfaction Index (LSI)-A questionnaire were included (men, 821; women, 1118). The mortality risk for the period up to December 2005 was measured using the Cox Proportional Hazard Model. RESULTS: When the relationship between LSI and mortality was evaluated in men, the unsatisfied group with lower LSI scores showed a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.83) than the satisfied group with higher LSI scores. In women, the unsatisfied group showed a significantly higher risk of all-cause mortality (HR, 1.51; 95% CI, 1.18-1.92) and cardiovascular mortality (HR, 2.23; 95% CI, 1.30-3.85) than the satisfied group. CONCLUSION: We found that elderly people with a lower LSI score, regardless of gender, were at risk of increased mortality from all causes, and low LSI score was also associated with cardiovascular mortality.

Effects of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men: the KARE study.

Adiponectin is secreted exclusively by adipocytes. Adiponectin is regulated by obesity, smoking, and genetic factors, including CDH13, which may contribute to development of diseases such as cardiovascular disease. Therefore, we aim to explore the joint effect of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men. This study included 1,570 Korean men aged 40-69 years who participated in the KARE cohort study (community-based cohorts, South Korea) from 2001. Hypoadiponectinemia was defined as the lowest quartile of adiponectin. In this study, individuals with at least one at-risk allele, the T allele, had an increased risk for hypoadiponectinemia, particularly current smokers with at least one T allele together with obesity when compared to those without the T allele. In addition, individuals with the TT genotype of CDH13 rs3865188, as well as obesity, were significantly associated with a 1.8-fold (odds ratio (OR) = 9.4, 95% confidence interval (CI) = 4.4-19.6, P < 0.001) increased risk for hypoadiponectinemia compared to individuals with the TT genotype of CDH 13 rs3865188 and normal waist circumference (WC) (OR = 5.1, 95% CI = 3.5-7.6, P < 0.001). However, in the joint effect of smoking and obesity, current smokers with the TT genotype of CDH13 rs3865188, as well as obesity, were significantly associated with a 6.2-fold (OR = 24.2, 95% CI = 3.0-196.6, P < 0.001) increased risk for hypoadiponectinemia compared to nonsmokers with the TT genotype of CDH 13 rs3865188 with normal WC (OR = 3.9, 95% CI = 1.7-9.3, P < 0.001). This study suggested that the association between CDH13 and adiponectin can be modified by lifestyle factors, such as smoking and obesity, among Korean men.