The association between COVID-19 vaccine/infection and new-onset asthma in children - based on the global TriNetX database.

INTRODUCTION: The COVID-19 pandemic has underscored the importance of its potential long-term health effects, including its link to new-onset asthma in children. Asthma significantly impacts children's health, causing adverse outcomes and increased absenteeism. Emerging evidence suggests a potential association between COVID-19 infection and higher rates of new-onset asthma in adults, raising concerns about its impact on children's respiratory health. METHODS: A retrospective cohort study design was employed, using electronic medical records from the TriNetX database, covering January 1, 2021, to December 31, 2022. Two cohorts of children aged 5 to 18 who underwent SARS-CoV-2 RT-PCR testing were analyzed: unvaccinated children with and without COVID-19 infection, and vaccinated children with and without infection. Propensity score matching was used to mitigate selection bias, and hazard ratio (HR) and 95% CI were calculated to assess the risk of new-onset asthma. RESULTS: Our study found a significantly higher incidence of new-onset asthma in COVID-19 infected children compared to uninfected children, regardless of vaccination status. In Cohort 1, 4.7% of COVID-19 infected children without vaccination developed new-onset asthma, versus 2.0% in their non-COVID-19 counterparts within a year (HR = 2.26; 95% CI = 2.158-2.367). For Cohort 2, COVID-19 infected children with vaccination showed an 8.3% incidence of new-onset asthma, higher than the 3.1% in those not infected (HR = 2.745; 95% CI = 2.521-2.99). Subgroup analyses further identified higher risks in males, children aged 5-12 years, and Black or African American children. Sensitivity analyses confirmed the reliability of these findings. CONCLUSION: The study highlights a strong link between COVID-19 infection and an increased risk of new-onset asthma in children, which is even more marked in those vaccinated. This emphasizes the critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children, advocating for thorough strategies to manage and prevent asthma amidst the pandemic.

Menopausal hormone therapy decreases the likelihood of diabetes development in peri­menopausal individuals with prediabetes.

BACKGROUND: The influence of menopausal hormone therapy (MHT) on the probability of developing diabetes mellitus in individuals with prediabetes remains uncertain. METHODS: This retrospective cohort study, utilizing the TriNetX U.S. Collaborative Network, investigated cohorts, implemented propensity score matching, and analyzed outcomes associated with diabetes mellitus. The study focused on individuals aged 46-60 with prediabetes prior to menopause, categorizing them into MHT and non-MHT groups. Further stratified analyses, including variables such as age and race, were conducted to thoroughly examine potential variations in outcomes. RESULTS: The study involved 6566 individuals (MHT and non-MHT), with propensity score matching ensuring balanced cohorts. Over a 20-year follow-up, the MHT group demonstrated a lower incidence of diabetes mellitus compared to the non- MHT group, with a Hazard Ratio of 0.693 (95 % CI: 0.577, 0.832). Stratified analyses revealed age-specific nuances, with significant protective effects in individuals aged 46-50 and 55-60. Additionally, ethnicity played a role, with MHT demonstrating significant benefits in White individuals but not in the Black or Asian populations. BMI analysis indicated a significant risk reduction with MHT in individuals with BMI less than or equal to 24.9 and 25-29.9 kg/m 2, but not in those with BMI greater than or equal to 30 kg/m 2. CONCLUSION: In our study, we demonstrate a sustained 20-year decrease in the risk of diabetes among premenopausal individuals with prediabetes who undergo menopausal hormone therapy.

Spine, hip, and femoral neck bone mineral density in relation to vegetarian type and status among Taiwanese adults.

We determined the association of vegetarian type and status with bone mineral density (BMD) Z-scores at the spine, hip, and femoral neck. Compared to non-vegetarians, current vegetarians, especially vegans, lacto-vegetarians, and lacto-ovo-vegetarians had lower Z-scores at multiple sites. Sole reliance on a vegetarian diet might be detrimental to the bone. PURPOSE: The impact of vegetarian diets on BMD is contentious. We determined the association of vegetarian type and status with the spine, hip, and femoral neck BMD Z-scores. METHODS: We analyzed data from 20,110 Taiwan Biobank volunteers. BMD was measured using dual-energy X-ray absorptiometry (DXA). The vegetarian status (non-, former, and current vegetarians) and type (non-vegetarians, ovo-vegetarians, lacto-vegetarians, lacto-ovo-vegetarians, and vegans) were determined using questionnaires. RESULTS: The participants consisted of 12,910 women and 7200 men, with a mean age of 55.5 years. Based on vegetarian status (reference: non-vegetarians), current vegetarians had significantly lower BMD Z-scores at the spine (unstandardized regression coefficient, B = - 0.195, p = 0.006), left hip (B = - 0.125, p = 0.008), and right hip (B = - 0.100, p = 0.027), respectively. Based on vegetarian status and type (reference: non-vegetarians), current vegans and non-vegans had notably lower BMD Z-scores at specific skeletal sites. For non-vegans, the BMD Z-scores were significant at the spine (B = -0.184, p = 0.010), left hip (B = - 0.124, p = 0.010), and left femoral neck (B = - 0.125, p = 0.012). For current vegans, however, the BMD Z-scores were significant only at the right hip (B = - 0.232; p = 0.028). Nonetheless, after stratifying vegetarian diet into more subgroups, current vegans exhibited a significant reduction in BMD Z-scores at the spine and right hip, with B-coefficients of - 0.326 and - 0.238, respectively. Current lacto-vegetarians also had significantly lower Z-scores (p < 0.05) at the spine (B = - 0.459), left hip (B = - 0.313), and right hip (B = - 0.214). Moreover, current lacto-ovo-vegetarians had significantly lower Z-scores at the spine (B = - 0.175) and left hip (B = - 0.115). CONCLUSION: Current vegetarians, particularly vegans, lacto-vegetarians, and lacto-ovo-vegetarians, demonstrated significantly lower BMD Z-scores at various skeletal sites compared to non-vegetarians. Sole reliance on a vegetarian diet might be detrimental to the bone.

Interactive Association Between CYP2C9 rs2860905 Polymorphism and Atrial Fibrillation on Ischemic Stroke in Taiwan Biobank Participants.

PURPOSE: Ischemic stroke accounts for approximately 85% of all strokes. Risk factors include atrial fibrillation, metabolic disorders, and genetic and lifestyle factors. There is limited evidence to support the association between atrial fibrillation and the risk of ischemic stroke based on genetic variants. We assessed the relationship between ischemic stroke and atrial fibrillation among participants in Taiwan Biobank (TWB) based on the rs2860905 variant of the cytochrome P450 Family 2 Subfamily C Member 9 (CYP2C9) gene. MATERIALS AND METHODS: Using logistic regression analysis, we estimated the odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke among 17,726 biobank adults recruited from 2008 through 2015. RESULTS: Of the eligible participants (n = 17,726), 906 were identified with ischemic stroke. Atrial fibrillation was positively associated with ischemic stroke (OR=3.70; 95% CI, 2.21-6.20), whereas the rs2860905 variant was not. The OR for ischemic stroke among those with GA/AA genotype was 1.00 (95% CI, 0.82-1.22) compared to those with the GG genotype. Based on the genotype-stratified analysis, the OR for ischemic stroke was 4.68 (95% CI, 2.70-8.09) among individuals with GG genotype who had atrial fibrillation compared to those who did not. CONCLUSION: These results demonstrate that the GG genotype of the CYP2C9 rs2860905 variant appears to enhance the risk of ischemic stroke among adults in Taiwan. It could be essential to factor this genotype-specific contributor to ischemic stroke into clinical and experimental investigations of the disease in Taiwan.

Peripheral Vascular Disease Susceptibility Based on Diabetes Mellitus and rs17367504 Polymorphism of the MTHFR Gene.

PURPOSE: Peripheral vascular disease (PVD) is a life-threatening condition affecting the lower extremities. Common risk factors include type 2 diabetes (T2D), hypertension, dyslipidemia, smoking, and older age. There is a little-documented research on the genetic basis of the disease in Taiwan. We examined the impact of T2D and the blood pressure-associated rs17367504 variant of the Methylenetetrahydrofolate reductase (MTHFR) gene on PVD risk. MATERIALS AND METHODS: In this population-based association study, we linked data from 8992 participants in Taiwan Biobank (TWB) to their medical records in the National Health Insurance Research Database (NHIRD). Participants were 30 to 70 years old at recruitment and included those assessed between 2008 and 2015. We tested for association of PVD with rs17367504 and T2D using multiple logistic regression models. The rs17367504 variant was assessed using the Axiom-Taiwan Biobank Array Plate (TWB chip: Affymetrix, Inc., Santa Clara, CA, USA). RESULTS: Among cases with T2D (n = 1294), 158 (12.21%) were identified with PVD. T2D was associated with PVD (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.21-1.91; p<0.001) whereas rs17367504 variant was not (OR, 0.96; CI, 0.76-1.21; p = 0.728 in AG/GG compared to AA homozygotes). However, T2D and rs17367504 had an interactive effect on PVD (p for interaction = 0.0076). Results from our stratified analyses displayed OR of 1.75 (CI, 1.35-2.26; p<0.001) in AA individuals with DM and 0.94 (CI, 0.56-1.58; p = 0.811) in AG+GG individuals with T2D. Using the AA genotype and no T2D as the reference group, the respective OR of PVD was 1.77 (CI, 1.38-2.28; p<0.001) in AA individuals with T2D; 1.18 (CI, 0.91-1.55; p = 0.215) in AG+GG individuals with no T2D, and 1.03 (CI, 0.66-1.60; p = 0.892) in AG+GG individuals with T2D . CONCLUSION: We found that type 2 diabetes was associated with increased risk of peripheral vascular disease, particularly in AA genotype carriers of the rs17367504 variant in Taiwan.

Interaction between Coffee Drinking and TRIB1 rs17321515 Single Nucleotide Polymorphism on Coronary Heart Disease in a Taiwanese Population.

A complex interplay of several genetic and lifestyle factors influence coronary heart disease (CHD). We determined the interaction between coffee consumption and the tribbles pseudokinase 1 (TRIB1) rs17321515 variant on coronary heart disease (CHD). Data on CHD were obtained from the National Health Insurance Research Database (NHIRD) while genotype data were collected from the Taiwan Biobank (TWB) Database. From the linked electronic health record data, 1116 individuals were identified with CHD while 7853 were control individuals. Coffee consumption was associated with a lower risk of CHD. The multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) was 0.84 (0.72-0.99). Association of CHD with the TRIB1 rs17321515 variant was not significant. The OR (95% CI) was 1.01 (0.72-0.99). There was an interaction between TRIB1 rs17321515 and coffee consumption on CHD risk (p for interaction = 0.0330). After stratification by rs17321515 genotypes, coffee drinking remained significantly associated with a lower risk of CHD only among participants with GG genotype (OR, 0.62; 95% CI, 0.45-0.85). In conclusion, consumption of coffee was significantly associated with a decreased risk of CHD among Taiwanese adults with the TRIB1 GG genotype.

Combination of Exercise and Vegetarian Diet: Relationship with High Density-Lipoprotein Cholesterol in Taiwanese Adults Based on MTHFR rs1801133 Polymorphism.

We examined the association between high-density lipoprotein cholesterol (HDL-C), and exercise and vegetarian diets, in Taiwanese adults, based on the Methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism. Using regression models, we analyzed historical data collected from 9255 Taiwan Biobank (TWB) participants from 2008 through 2015. Exposure to exercise was associated with higher HDL-C (ß = 1.0508 and 1.4011 for GG and GA + AA individuals, respectively), whereas a vegetarian diet was associated with lower HDL-C (ß = -6.2793 and -4.6359 for those with GG and GA + AA genotype, respectively). We found an interaction between exercise and diet among GG individuals (p = 0.0101). Compared with no exercise/no vegetarian diet, vegetarian diet/no exercise was associated with a 5.1514 mg/dl reduction in HDL-C among those with GG genotype (ß = -5.1514, p < 0.0001) and a 4.8426 mg/dl reduction (ß = -4.8426, p < 0.0001) among those with GA + AA genotype. Vegetarian diets in combination with exercise predicted a 6.5552 mg/dl reduction in HDL-C among GG individuals (ß = -6.5552) and a 2.8668 mg/dl reduction among GA + AA individuals (p < 0.05). These findings demonstrated that vegetarian diet alone was associated with lower HDL-C, no matter the rs1801133 genotype. However, the inclusion of regular exercise predicted much lower levels among GG individuals, whereas levels among GA + AA individuals were relatively higher.

Association between osteoporosis and menopause in relation to SOX6 rs297325 variant in Taiwanese women.

OBJECTIVE: Osteoporosis, the most prevalent bone disorder in humans, is a global public health issue and its relationship with menopause is well-established. The interaction between menopause and genes on osteoporosis risk is, however, yet to be fully elucidated. We assessed the association between menopause and osteoporosis in relation to the SOX6 rs297325 variant in Taiwanese women. METHODS: There were 7,581 female participants, aged 30 to 70 years old. Information on SOX6 rs297325 and menopause were obtained from the Taiwan Biobank Database while that on osteoporosis was obtained from the National Health Insurance Research Database. RESULTS: Menopause but not SOX6 rs297325 was significantly associated with a higher risk of osteoporosis (odds ratio [OR] = 1.48; 95% confidence interval [CI] = 1.04-2.10). The interaction between menopause and rs297325 on osteoporosis was significant (P = 0.0216). After stratification by rs297325 genotypes, the risk of osteoporosis was significantly higher in menopausal women having the TT + CC genotype (OR = 2.02; 95% CI = 1.21-3.38). After stratification by menopausal status and rs297325 genotypes, the OR; 95% CI was 0.62; 0.38 to 0.99 in premenopausal women with the TC + CC genotype and 1.24; 0.82 to 1.88 in menopausal women with the TC + CC genotype. CONCLUSION: SOX6 rs297325 was not significantly associated with osteoporosis but might have modulated the association between menopause and osteoporosis. The risk of osteoporosis was higher in menopausal women with the TC + CC genotype but lower in premenopausal women with the TC + CC genotype.

Vegetarian Diets along with Regular Exercise: Impact on High-Density Lipoprotein Cholesterol Levels among Taiwanese Adults.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30-70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (ß = -5.705; p = 0.001) followed by lacto-ovo vegetarians (ß = -3.900; p < 0.001) and former vegetarians (ß = -0.329; p = 0.475). The test for trend was significant (p < 0.001). After categorization by exercise modalities, the ß-value was -13.984 for strict vegetarians, -4.419 for lacto-ovo vegetarians, and -1.864 for former vegetarians, respectively (p < 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

Interaction between Sex and LDLR rs688 Polymorphism on Hyperlipidemia among Taiwan Biobank Adult Participants.

Hyperlipidemia is one of the strong risk factors for ischemic heart disease. Using the Taiwan Biobank (TWB) database, we evaluated the risk of hyperlipidemia and its interaction with sex and rs688 polymorphism on the low-density lipoprotein receptor (LDLR) gene. Data collection in the biobank started in 2008 and is ongoing. Data analysis was performed on the participants' data collected between 2008 and 2015. In general, 27.92% of the 9237 female participants and 32.65% of the 8690 male participants were identified with hyperlipidemia. Compared to the C/C genotype, C/T and T/T genotypes were not significant risk factors for hyperlipidemia (OR = 1.061, CI: 0.976-1.153 for C/T and OR = 1.052, CI: 0.845-1.309 for T/T genotype) in the general model. However, there was a significant interaction between sex and rs6888 on hyperlipidemia risk (p-interaction = 0.0321). With the male sex/CC genotype being the reference group, only the female sex/CT and T/T genotypes were closely associated with hyperlipidemia, with respective ORs of 1.153 (CI: 1.014-1.311) and 1.423 (CI: 1.056-1.917). Our data indicate that rs688 C/T and T/T genotypes may be associated with increased risk of hyperlipidemia in Taiwanese women. These findings may be relevant in lipid-modification therapy.

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.

Association between coarse particulate matter (PM10-2.5) and nasopharyngeal carcinoma among Taiwanese men.

The nasopharyngeal tract traps mainly coarse particles in inhaled air. Soluble carcinogenic compounds, endotoxins, and trace metals contained in these particles are potential causes of inflammation and oxidative stress which could enhance carcinogenesis. The aim of this study was to determine the association between coarse particulate matter (PM10-2.5) and nasopharyngeal cancer (NPC). A total of 521,098 men (355 cases and 520,743 non-cases), aged ≥40 years were included in this study. Data were retrieved from the Taiwan Cancer Registry, the Adult Preventive Medical Services Database, and the Air Quality Monitoring Database. PM10-2.5 was significantly associated with a higher risk of NPC after adjusting for SO2, NOx, O3, age, body mass index, smoking, alcohol drinking, betel nut chewing, exercise, hypertension, diabetes, and hyperlipidemia. With PM10-2.5<20.44 µg/m3 as the reference, the ORs and 95% CIs were 1.47; 1.03-2.11, 1.34; 0.94-1.91, and 1.68; 1.16-2.44 for 20.44≤PM10-2.5<24.08, 24.08≤PM10-2.5<29.27, and PM10-2.5≥29.27 µg/m3, respectively. PM10-2.5 remained significantly associated with a higher risk of NPC after further adjustments were made for the aforementioned covariates and PM2.5 The ORs; 95% CIs were 1.42; 0.96 to 2.12, 1.41; 0.94 to 2.10, and 1.71; 1.10 to 2.66 for 20.44≤PM10-2.5<24.08, 24.08≤PM10-2.5<29.27, and PM10-2.5≥29.27 µg/m3, respectively. In conclusion, PM10-2.5 was significantly associated with a higher risk of NPC in Taiwanese men.

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.

Association between chronic obstructive pulmonary disease and PM2.5 in Taiwanese nonsmokers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world. Not much is known regarding the influence of non-smoking-related risk factors on COPD in Taiwan. We examined the relationship between exposure to particulate matter <2.5 µm (PM2.5) and COPD among nonsmokers in Taiwan. METHODS: This population-based study involved 3941 nonsmoking Taiwanese adults who were recruited in the Taiwan Biobank project between 2008 and 2015. Air pollution data between 2006 and 2011 were obtained from the air quality monitoring database (AQMD). COPD was the outcome of interest and was identified using the National health insurance Research Database (NHIRD). The data were analyzed using multiple logistic regression models. RESULTS: Compared with the lowest quartile (PM2.5 = 29.38), exposure to PM2.5 in the highest quartile (>38.98 µg/m3) was significantly associated with COPD (OR, 1.29; CI 1.01-1.65) after multivariate adjustments. However, exposures to concentrations of 32.07-38.98 µg/m3 (OR, 1.12 CI 0.88-1.44) and 29.38-32.07 µg/m3 (OR, 1.09 CI 0.84-1.41) showed positive but non-significant associations. However, the test for trend was significant (Ptrend = 0.043). The ORs for exposure to sulfur dioxide (SO2), ozone (O3), carbon monoxide (CO) and NOx (nitrogen monoxide (NO were not significant. CONCLUSIONS: Based on our data, exposure to PM2.5 at concentrations greater than 38.98 µg/m3 increased susceptibility to COPD among Taiwanese nonsmokers. Combatting COPD would involve integrating tobacco control and pollution management strategies.

SOX2 promoter hypermethylation in non-smoking Taiwanese adults residing in air pollution areas.

BACKGROUND: Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter < 2.5 µm (PM2.5). METHODS: A total of 1142 individuals aged 30-70 years were recruited. Data on SOX2 methylation, residence, age, and exposure to second-hand smoke (SHS) among others were extracted from the Taiwan Biobank dataset (2008-2015). After excluding former and current smokers, alongside those with incomplete information, a total of 461 non-smokers comprising 176 men and 285 women were included in the study. Participants' residences were grouped under northern and central/southern areas because air pollution (PM2.5) is lower in northern compared to central and southern areas. RESULTS: The methylation levels in men (0.16310 ± 0.01230) and women (0.15740 ± 0.01240) were significantly different (P < .0001). In both sexes, the SOX2 promoter region was shown to be significantly hypermethylated in central and southern areas compared with the northern areas. The regression coefficient (ß) was 0.00331 (P = 0.0257) in men and 0.00514 (P < .0001) in women. CONCLUSION: SOX2 was significantly hypermethylated in both men and women residing in central and southern areas. The consistency in the results for both sexes shows that SOX2 promoter methylation could serve as a potential biomarker for industrial air pollution exposure. Moreover, it might reflect predisposition to cancer. Hence, healthy non-smokers at precancerous stages who have not been clinically diagnosed could be identified.

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.

Association of type 2 diabetes with liver cirrhosis: a nationwide cohort study.

BACKGROUND: The link between the subcategories of liver cirrhosis and type 2 diabetes is not well known. We investigated the association of type 2 diabetes mellitus with alcoholic cirrhosis and cirrhosis without alcohol. METHODS: This nationwide cohort study used the Taiwan National Health Insurance Research Database. Cirrhotic individuals and their matched controls were identified from 2001-2008. In all, 9 313 cirrhotic patients aged 20 years or older were matched by age, sex, and index date with the non-cirrhotic individuals (n = 37 252). Cirrhosis was categorized into alcoholic cirrhosis and cirrhosis without alcohol. Type 2 diabetes mellitus was identified from January 2001- December 2011. RESULTS: The incidence densities (per 1 000 person-months) of type 2 diabetes were as follows: 1.14 (95% CI: 1.09-1.20) in the non-cirrhotic group, 1.88 (CI 1.76-2.01) in patients with cirrhosis, 1.62 (CI 1.48-1.78) in patients with cirrhosis without alcohol, and 2.92 (CI 2.64-3.23) in patients with alcoholic cirrhosis. The adjusted hazards ratio (aHR) for type 2 diabetes mellitus among cirrhotic individuals was 0.774 (CI: 0.715-0.8934). Alcoholic cirrhotic men had a significantly higher risk of type 2 diabetes (aHR 1.182, CI: 1.046-1.335) compared with non-cirrhotic individuals. Increased risks were seen in men (aHR 1.690; CI: 1.455-1.963) and women (aHR 1.715; CI: 1.113-2.645) with alcoholic cirrhosis compared to those with cirrhosis without alcohol. CONCLUSIONS: This study indicates that alcoholic cirrhosis is a significant risk factor for type 2 diabetes mellitus compared with cirrhosis without alcohol.

Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD.

BACKGROUND: Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk. However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD). TB and pneumonia have increased lung cancer risk. The association between post-ICS pulmonary infections and lung cancer remains unclear. METHODS: We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database. Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use. RESULTS: The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia. For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia. CONCLUSIONS: COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer. Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions.

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma.

PURPOSE: To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. METHODS: The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. RESULTS: A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22-5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73-2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84-6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57-2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63-1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05-2.32; p = 0.261) for pneumonia+ TB, respectively. CONCLUSIONS: Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

Effect of coexisting diabetes mellitus and chronic kidney disease on mortality of cirrhotic patients with esophageal variceal bleeding.

BACKGROUND: Esophageal variceal bleeding (EVB) is a serious and common complication of cirrhosis. Diabetes mellitus (DM) and chronic kidney disease (CKD) increase mortality in patients with cirrhosis. However, whether coexisting DM and CKD increase mortality in cirrhotic patients with EVB remains unclear. METHODS: We enrolled cirrhotic patients hospitalized with the first presentation of EVB from 2005 through 2010 using Longitudinal Health Insurance Database 2005. The hazard ratios (HRs) of 42-day and one-year EVB mortality were calculated using Cox regression model. RESULTS: We identified 888 patients hospitalized with the first presentation of EVB. Among the cirrhotic patients with EVB, all-cause mortality at 42-day and one-year were 21.3 and 45.0 %, respectively. The respective HRs for the 42-day and one-year mortality were 1.80 (95 % confidence interval [CI], 1.10-2.97) and 1.52 (95 % CI, 1.06-2.17) for patients with CKD and 0.79 (95 % CI, 0.57-1.10) and 0.88 (95 % CI, 0.71-1.09) for patients with DM. Specifically, coexisting CKD and DM increased the 42-day and one-year mortality with respective HRs of 1.99 (95%CI, 1.03-3.84) and 1.84 (95%CI, 1.14-2.98) compared with those without CKD and DM. The HRs for 42-day and 1-year mortality in female patients with DM and CKD were 4.03 (95%CI, 1.40-11.59) and 2.84 (95%CI, 1.31-6.14) respectively, and were 2.93 (95%CI, 1.14-7.57) and 2.42 (95%CI, 1.28-4.57) in male patients with DM and CKD. CONCLUSION: We identified that coexisting DM and CKD increased risk of mortality at 42 days and 1 year following EVB.