Apoptosis pathways and osteoporosis: An approach to genomic analysis.

BACKGROUND: Osteoporosis is a disease of the bone system that causes a decrease in skeletal density and degrades skeletal tissue. Decreased bone quality, so that bones are easily broken, damaged and fractured, is an important public health problem. Previous studies have shown that the maintenance of adult bone mass is not only due to changes in bone marrow and bone cells. By regulating apoptosis, they change the lifespan of each individual. This study influences understanding of the function of apoptosis in the pathogenesis of osteoporosis and the importance of controlling the mechanisms of osteoporosis. METHODS: On the National Institute of Biotechnology Information website, Gene Expression Omnibus (GEO) microarray data and GSE551495 GEO profiles were collected. The gene set enrichment analysis tool was used to confirm the enrichment of genetic sets in relation to the gene set. The collection of C2 gene sets is compiled from the KEGG (https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://www.kegg.jp/kegg/) online database and REACTOME (https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://reactome.org/) pathway analysis. The Search Tool for the Retrieval of Interaction Genes (STRING) website was used to construct and select proteins and genes. The comparative toxicological genomic database (CTD) tools can be used to predict the relationship between apoptosis, osteoporosis-related genes and interactions between central genes and osteoporosis. RESULTS: These results generally expand our understanding of the path of apoptosis in osteoporosis. We have discovered genes CASP9, CASP8, CASP3, BAX and TP53 associated with osteoporosis. In activation of KEGG apoptosis and REACTOME, caspase activation through the extrinsic apoptotic signaling pathway is characterized by the identification of a subcollection of C2. Other STRINGs show the formation of protein networks and central gene selection, and CTD can accurately predict the relationship between these apoptosis pathways and central genes. CONCLUSIONS: Our research has highlighted the importance of the osteoporosis pathway associated with osteoporosis apoptosis with several analytical approaches. These results have broadened our understanding of the pathways of osteoporosis apoptosis. It is particularly possible to predict the sensitivity and vulnerability to osteoporosis.

Risk of HBV infection among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan.

BACKGROUND: In July 1984, Taiwan officially began a nationwide hepatitis B virus (HBV) vaccination program where only infants born to HBsAg-positive mothers were vaccinated free of charge until June 1986. However, from July 1986, all infants were vaccinated against HBV. The impact of the July 1986 HBV vaccination program on first-time blood donors has not been exhaustively studied. We, therefore, determined the risk of HBV among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. METHODS: Initially, we recruited 857,310 first-time blood donors whose data were collected between 2013 and 2018 from 5 blood donation centers in Taiwan. However, we excluded donors with incomplete and outlying data (n = 12,213) and those born between July 1984 and June 1986 (n = 21,054). The final study participants comprised 9118 HBV positive and 814,925 HBV negative individuals. We divided the participants into two birth cohorts (born before and after July 1986) and assumed that those born before July 1986 were not vaccinated at birth while those born after July 1986 were vaccinated. RESULTS: The prevalence of HBV among those born before and after July 1986 was 4.53 and 0.25%, respectively. Individuals born after July 1986 had a lower risk of HBV than those born before July 1986. The adjusted odds ratio (OR), 95% confidence interval (CI) was 0.16, 0.13-0.19. Men had a higher risk of HBV than women (OR = 1.40, 95% CI = 1.34-1.47). The interaction between sex and birth date was significant (p-value = 0.0067). Stratification of participants by birth date revealed a higher risk of HBV in men compared to women in both birth cohorts. The OR, 95% CI was 1.47, 1.40-1.55 for those born before July 1986 but declined to 1.15, 1.02-1.29 for those born after July 1986. CONCLUSIONS: The risk of HBV was lower among those born after than those born before the July 1986 vaccination program. In both cohorts, the risk was high in men relative to women. The seemingly protective effect among those born after July 1986 was higher in women than men.

Relationship between BRSK1 rs12611091 variant and age at natural menopause based on physical activity.

OBJECTIVES: The rs12611091 variant in the BR serine/threonine kinase 1 gene is one of the variants previously associated with age at natural menopause. So far, this variant has not been replicated in Taiwanese women. The purpose of this study was to determine the association between rs12611091 and age at natural menopause based on physical activity. METHODS: A total of 1,758 women were eligible for analysis whose information about menopause was collected from the Taiwan Biobank. Multiple linear regression analysis was used for analysis. RESULTS: The mean age (standard deviation) at natural menopause was 50.82 (3.59) years. Of the eligible participants, 56.94% were rs12611091 CC carriers, 36.69% were TC carriers, and 6.37% were TT carriers. Compared to CC carriers, TC and TT carriers were associated with early menopause (ß = -0.42, P = 0.02 and -0.87, P = 0.01, respectively). There was a significant interaction between rs12611091 and physical activity (P for interaction = 0.02). Compared to rs12611091 CC carriers, TC and TT carriers who were physically inactive were significantly associated with earlier menopause (ß = -0.88, P < 0.01 and -1.25, P = 0.02, respectively). CONCLUSION: We demonstrated that rs12611091 variant was associated with age at natural menopause especially among inactive women in Taiwan. That is, women with TC and TT genotypes who were physically inactive were significantly associated with earlier natural menopause compared to those with CC genotype.

Online community collaborative map: A geospatial and data visualization tool for cancer data.

The aim of this study was to develop an online collaborative map to enable researchers to locate, explore, and share cancer data.This 2-scale (global and country-level) cancer map adopts a database-driven model, which was implemented using the Google Map Application Programming Interface (API) and asynchronous JavaScript and XML (AJAX) technology. Seven visualization techniques were used to present data. Data on worldwide cancer mortality between 1950 and 2013 were taken from the International Agency for Research on Cancer (IARC) database. Incidence data were from the IARC CI5plus database. Survival data were from the IARC SURVCAN study. Prevalence data between 1990 and 2017 were from the Institute for Health Metrics and Evaluation's (IHME) catalog while demographic data were from the World Bank Data Catalog. Cancer data for Taiwan between 1991 and 2016 were obtained from the Department of Health and Welfare. This study used visualization techniques that included: a choropleth map to display the prevalence of cancer; a tornado diagram to show the age-standardized mortality rates of all cancers among men and women in 2013; a treemap to show a ranking of cancer mortality data; a sunburst chart to show mortality rates of all cancers by gender; a line chart to show mortality trends for all cancers; a bar chart to show mortality and incidence rates and a heatmap to show variations in cancer across different countries.The world cancer map generated by this study can be accessed at http://worldmap.csmu-liawyp.tw. Country-level mortality data are presented as crude and age-standardized rates.We used visualization methodologies and constructed an easily maintainable web-based user interface with cancer data from administrative regions in 150 countries. This serves as a platform that allows researchers to manage and disseminate cancer data.

Methylation at cg05575921 of a smoking-related gene (AHRR) in non-smoking Taiwanese adults residing in areas with different PM2.5 concentrations.

BACKGROUND: DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. METHODS: Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008-2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30-70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. RESULTS: Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (ß = - 0.01003, P = 0.009 and ß = - 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. CONCLUSION: Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease.

Duration-response association between exercise and HDL in both male and female Taiwanese adults aged 40 years and above.

BACKGROUND: Exercise is an important cardiovascular risk reducing therapy. OBJECTIVE: The aim of this study was to assess the relationship between weekly exercise duration and high-density lipoprotein cholesterol (HDL-c) in Taiwanese men and women. METHODS: Data were retrieved from the dataset of the national adult preventive medical services which is recorded under the Health Promotion Administration (HPA). The lipid profiles of 194528 eligible participants aged 40 years and above who completed a questionnaire on recent health behavior including smoking, drinking, exercise and other factors in 2014 were determined. Weekly exercise durations of 0.0, <2.5 and ≥2.5 hours were classified as no, below recommended and recommended, respectively. The relationship between exercise and HDL-c was determined using linear regression. RESULTS: After multivariate adjustments, a duration-response association existed between exercise and HDL-c (P-trend <0.0001) in both sexes. Weekly exercise durations of <2.5 and ≥2.5 hours were both positively associated with HDL-c (P <0.0001) in both sexes. However, the associations were stronger in males than females in both exercise groups. Smoking (P <0.05) and BMI (P <0.0001) were negatively associated while drinking was positively associated with HDL-c in both sexes. CONCLUSION: This study demonstrated a duration-response association between exercise and HDL-c. Exercise at durations below the minimum weekly recommendation of 2.5 hours was positively associated with HDL-c.

Body mass index modulates the association between CDKAL1 rs10946398 variant and type 2 diabetes among Taiwanese women.

CDKAL1 rs10946398 is a type 2 diabetes (T2D)-associated variant. It is a new body mass index (BMI)-associated variant in Asian populations. We investigated the association between rs10946398 and T2D among 9908 participants aged 30-70 years based on BMI: normal weight; 18.5 ≤ BMI < 24 kg/m2, overweight; 24 ≤ BMI < 27 kg/m2, and obesity; BMI ≥27 kg/m2. The CC genotype conferred a higher risk of T2D than the CA genotype. The odds ratios (ORs) were 1.83; 95% confidence interval (CI) 1.49-2.26 and 1.20; 95% CI 1.02-1.40, respectively. The C allele was the significant risk allele compared with A allele (OR = 1.32; 95% CI 1.19-1.47). For normal, overweight and obese participants with CC genotype, the ORs were respectively 1.69; 95% CI 1.02-2.81, 2.34; 95% CI 1.50-3.66, and 1.58; 95% CI 1.02-2.45 among men and 1.22; 95% CI 0.67-2.22, 2.42; 95% CI 1.30-4.52, and 2.3; 95% CI 1.19-4.50 among women. The C allele ORs were higher in obese and overweight women. In conclusion, the rs10946398 CC/CA genotypes, as well as the C allele increased the risk of T2D. The ORs were higher in women who were overweight and obese than in those with normal weight. Nonetheless, significant results were prominent only among those with CC genotype and C allele.