Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study.

BACKGROUND: Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown. METHODS: The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined. RESULTS: Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04-0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18-0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42-0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49-0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27-0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68-0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32-0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81-0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONS: Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study.

BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (ß = 0.052, P = 0.002) and LDL (ß = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (ß = 0.240, P = 0.033) and LDL (ß = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION: Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Differences and Correlation Analysis of Birth Weight and Overweight/Obesity in Shanghai Twin Cohort.

The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case-control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future.

[Setting of logos on tobacco control information at outlets for retails and restaurants in 12 cities of China].

OBJECTIVE: To explore the setting of logos on tobacco control information at outlets for retails and restaurants in 12 selected cities of China. METHODS: For all the shops for retail of tobacco, alcohol, food and restaurants under survey in 333 blocks of 12 cities(Beijing, Tianjin, Shanghai, Qingdao, Hangzhou, Shaoxing, Suzhou, Nantong, Zhenjiang, Chengdu, Xining and Harbin), setting and contents of logos on tobacco control information, inside and outside them were examined. RESULTS: 45 700 objectives were included in the study. Among all types of retail shops, the identification rate of tobacco control information at the entrance and inside were 3.6% and 4.4%, with an overall identification rate as 7.0%. The overall rate at the entrance of all the restaurants was 4.6% which was larger than the ones at the retail shops. Our result showed that there were differences between cities and types of establishments and higher rates seen in the larger ones. Of all the places that having had placement of information on tobacco control, only 18.5% of them had put them both inside and outside. Slogans or images on "No Smoking" were the main forms of information but less than 10% of them would show signs as 'exclusive non-smoking'. CONCLUSION: Data from our survey showed that the identification rate of tobacco control information was at a low level in 12 cities, and differences were seen between cities, size of establishment, that called for improvement of the existing tobacco control policies in China.

[Relationship between the clustering of risk factors and the prevalence of hypertension in the community residents living in Shanghai].

OBJECTIVE: To study the association between the clustering manifestation of factors as overweight and central obesity, family heredity, immoderate alcohol drinking, tobacco smoking, hyperlipidemia, hyperglycemia and the prevalence of hypertension. METHODS: Data was from a program related to the comprehensive prevention and control strategies on cardiac-cerebral vascular disease carried out in the communities of Shanghai, to describe the relationship between the clustering of risk factors and hypertension. This program included 15 158 people with complete data at the age of 35 - 74, from 2008 - 2011. Both single factor and multi-factor analysis were used and longitudinal study was performed to further explore the causal relationship. RESULTS: The overall prevalence of hypertension at the baseline survey was 41.9%. The associated ORs (age-adjusted) of hypertension parallelly increased with the number of risk factors under clustering. The associated OR of the males with 1, 2, 3, 4 as well as 5 and above risk factors were 3.157 [95% confidence interval (CI): 2.152 - 4.630], 6.428 (95%CI: 4.435 - 9.319), 11.797 (95%CI: 8.135 - 17.105), 19.723 (95%CI: 13.414 - 29.000), 33.051 (95%CI: 21.449 - 50.930) respectively. In females with 1, 2, 3 as well as 4 risk factors, the associated ORs were 2.917 (95%CI: 2.374 - 3.585), 6.499 (95%CI: 5.307 - 7.959), 15.717 (95%CI: 12.609 - 19.591) and 31.719 (95%CI: 21.744 - 46.270), respectively. For longitudinal study, the 2-year incidence of hypertension in males and females were 1.9% and 1.6%, respectively. Compared to those people without risk factors, the incidence was higher in the people with a larger number of clustering. When the clustering number reaching 2 or 3 in females, the relative risk (RR) were 2.111 (95%CI: 1.024 - 4.350) and 3.000 (95%CI: 1.287 - 6.995) respectively, with statistically significant difference. CONCLUSION: The risk of hypertension parallelly increased with the clustering number of relevant risk factors. Comprehensive prevention and control on related risk factors was required.

Interactions of renin-angiotensin system gene polymorphisms and antihypertensive effect of benazepril in Chinese population.

AIM: Angiotensin-converting enzyme inhibitors are widely used antihypertensive drugs with individual response variation. We studied whether interactions of AGT, AGTR1 and ACE2 gene polymorphisms affect this response. MATERIALS & METHODS: Our study is based on a 3-year field trial with 1831 hypertensive patients prescribed benazepril. Generalized multifactor dimensionality reduction was used to explore interaction models and logistic regressions were used to confirm them. RESULTS: A two-locus model involving the AGT and ACE2 genes was found in males, the sensitive genotypes showed an odds ratio (OR) of 1.9 (95% CI: 1.3-2.8) when compared with nonsensitive genotypes. Two AGT-AGTR1 models were found in females, with an OR of 3.5 (95% CI: 2.0-5.9) and 3.1 (95% CI: 1.8-5.3). CONCLUSION: Gender-specific gene-gene interactions of the AGT, AGTR1 and ACE2 genes were associated with individual variation of response to benazepril. Further studies are needed to confirm this finding.

[Effects of diet and physical activity factors on blood pressure in nine provinces of China: a longitudinal analysis].

OBJECTIVE: To study the effects of diet and physical activity factors on blood pressure in nine provinces, using the multilevel model. METHODS: Data was collected in the China Health and Nutrition Survey (CHNS). A total of 6706 men and 7140 women aged above 18 who attended at least one of the surveys in the year of 1997, 2000, 2004 and 2006 were selected, and a two-level male and female random intercept-slope growth models were applied to estimate the relationship between the intake of daily salt, vegetable, fruit, fat, protein as well as the time spent on the moderate or heavy physical activity and blood pressure. RESULTS: After controlling for age, education, BMI, drinks and total energy intake, mean of the daily salt intake per person was positively associated with systolic blood pressure in women (ß = 0.0481, s(x(-)) = 0.0178, P < 0.01). Mean of the daily vegetable intake per person was negatively associated with systolic blood pressure in men and women, with the regression coefficients as -0.0063, -0.0068 respectively, indicating that if mean of the daily vegetable intake per person increased by 100 g, the systolic blood pressure would decrease by 0.6 mm Hg (1 mm Hg = 0.133 kPa) or more. In addition, the daily vegetable intake was also negatively associated with diastolic blood pressure (P < 0.01). Daily fruit intake was negatively associated with systolic blood pressure both in men and women, with regression coefficients as -0.0029 and -0.0031 respectively. Time spent on the moderate or heavy physical activity was also negatively associated with systolic blood pressure in both men and women, and diastolic blood pressure in women (P < 0.05). No relationship was found between daily fat, protein intake and blood pressure. CONCLUSION: Daily salt, vegetable, fruit intake, time spent on the moderate or heavy physical activity were associated with blood pressure in both men and women. Programs on integrated lifestyle modifications including dietary salt reduction, eating more vegetable and fruits, increasing physical activity level, plus weight control were critical for the control of high blood pressure.

[Correlation of angiotensin-converting enzyme 2 gene polymorphism with antihypertensive effects of benazepril].

OBJECTIVE: To explore the correlation of rs2106809 from angiotensin-converting enzyme 2 gene with antihypertensive effects of benazepril, as well as its interactions with polymorphisms of angiotensinogen(AGT) and angiotensin II type 1 receptor(AGTR1) gene. METHODS: Correlation between rs2106809 and blood pressure reduction was estimated based on a field trail with 1 831 hypertensive patients using benazepril for 2 weeks. Generalized multifactor dimensionality reduction (GMDR) was used to explore the interactions of rs2106809 and 8 single nucleotide polymorphisms (SNPs) of AGTR1 gene and 3 SNPs of AGT gene. RESULTS: rs2106809 was found to be associated with reduction in systolic blood pressure and pulse pressure in women, as well as pulse pressure reduction in men. T allele carriers presented more blood pressure reduction (1.4, 1.3 and 0.9 mmHg/T allele respectively). Gene-gene interactions involving rs2106809 were found in systolic blood pressure reduction of men, and the response to benazepril of non-sensitive genotypes carriers was 8.2 (95% confidence interval: 6.6-9.7) mmHg, lower than that of sensitive genotypes carriers. CONCLUSION: rs2106809 might act as an independent influencing factor or component of gene-gene interaction in blood pressure reducing effects of benazepril.

Associations between variants of the 8q24 chromosome and nine smoking-related cancer sites.

Recent genome-wide association studies identified key single nucleotide polymorphisms (SNPs) in the 8q24 region to be associated with prostate cancer. 8q24 SNPs have also been associated with colorectal cancer, suggesting that this region may not be specifically associated to just prostate cancer. To date, the association between these polymorphisms and tobacco smoking-related cancer sites remains unknown. Using epidemiologic data and biological samples previously collected in three case-control studies from U.S. and Chinese populations, we selected and genotyped one SNP from each of the three previously determined "regions" within the 8q24 loci, rs1447295 (region 1), rs16901979 (region 2), and rs6983267 (region 3), and examined their association with cancers of the lung, oropharynx, nasopharynx, larynx, esophagus, stomach, liver, bladder, and kidney. We observed noteworthy associations between rs6983267 and upper aerodigestive tract cancers [adjusted odds ratio (ORadj), 1.69; 95% confidence interval (95% CI), 1.28-2.24], particularly in oropharynx (ORadj, 1.80; 95% CI, 1.30-2.49) and larynx (ORadj, 2.04; 95% CI, 1.12-3.72). We also observed a suggestive association between rs6983267 and liver cancer (ORadj, 1.51; 95% CI, 0.99-2.31). When we stratified our analysis by smoking status, rs6983267 was positively associated with lung cancer among ever-smokers (ORadj, 1.45; 95% CI, 1.05-2.00) and inversely associated with bladder cancer among ever-smokers (ORadj, 0.35; 95% CI, 0.14-0.83). Associations were observed between rs16901979 and upper aerodigestive tract cancer among never-smokers and between rs1447295 and liver cancer among ever-smokers. Our results suggest variants of the 8q24 chromosome may play an important role in smoking-related cancer development. Functional and large epidemiologic studies should be conducted to further investigate the association of 8q24 SNPs with smoking-related cancers.