HTRA1 Variants and the Interaction with Smoking Confer the Genetic Susceptibility to Ischemic Stroke.

High temperature requirement protein A1 (HtrA1) was identified as the causative gene of autosomal recessive arteriopathy and associated with lacunar ischemic stroke (IS) in European. This study aimed at evaluating the association of HTRA1 with IS and four tagging single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of 4,098 Chinese. The mRNA level of HTRA1 in 72 IS cases and 72 hypertension controls were measured and compared. In whole population, SNP rs2268350 (C>T) was significantly associated with IS incidence (P=0.034). Stratification analysis observed significant association of rs2268350 in male, smoking and drinking populations, rs2672587 (C>G) in smoking and nonsmoking populations and rs3793917 (C>G) in smoking, nonsmoking and nondrinking populations with stroke respectively (P<0.05). The additive interaction and multiplicative interaction between rs2268350 and smoking were both of significant (P<0.05) after adjustment for the covariates. There was a cumulated risk of IS among genotypes of rs3793917 (P=0.009) and rs2672587 (P=0.047) in smoking population. The mRNA level of HTRA1 in non-smokers with rs2268350 CC was significantly higher than smokers with rs2268350 CT/TT (P=0.046) in IS cases. Our findings support that HTRA1 confers the genetic susceptibility to IS and smoking might modify the genetic effect of HTRA1 on IS by suppressing HTRA1 mRNA expression.

Impact of physical exercise intervention and PPARγ genetic polymorphisms on cardio-metabolic parameters among a Chinese youth population.

OBJECTIVE: Physical inactivity inChinese youth students particularly in senior high schools, who participate inthe National Higher Education Entrance Examination (NCEE) is very common. Inorder to explore the beneficial effects from physical exercise and education afterNCEE, we performed a Physicalexercise Intervention Program in the Youth (PiPy) to evaluate the interaction with PPARγ genetic variants on cardiovascular and metabolicparameters. METHODS: A total of 772 freshmen (males 610/females162) from high schools to university were recruited into the PiPy cohort, which was designedaccording to the National Student Health Standards in China. Anthropometric data were collected, whilephysical activities and body composition at the baseline of PiPy cohort weremeasured with SECAprotocols. Eighttagged single nucleotide polymorphisms (SNPs) in the PPAR γ gene were genotyped with TaqMan allelicdiscrimination. RESULTS: After physical exercise intervention forthree months, in parallel with increased physical activities, BMI and skeletalmuscle content in all subjects was enhanced, while heart rate and bloodpressures were decreased. Furthermore, SNPs in 5'-UTR of the PPARγ gene, including rs2920502, rs9817428 and rs2972164, were found to be associated with the changes of BMI. Body weight in the subjects with BMI <18.5and 18.5-23.9 kg/m2 were increased, while the obese subjects (BMI ≥24.0 kg/m2) decreased. CONCLUSION: The present study for the first timedemonstrated that the PiPy could improve cardio-metabolic parameters such asheart rate, blood pressures and BMI for Chinese youth students after NCEE, inwhich the genetic interactive effects of PPAR γ should be included into obesityintervention.

A comprehensive contribution of genetic variations of the insulin-like growth factor 1 signalling pathway to stroke susceptibility.

BACKGROUND AND AIMS: The insulin-like growth factor (IGF)-1 signalling pathway has been implicated in the pathogenesis of atherosclerosis; however, the mechanism underlying its role in stroke remains unexplained. Herein, we aimed to explore the effects of genetic polymorphisms in the IGF1 pathway on stroke in the Chinese Han population. METHODS: Twenty-six single-nucleotide polymorphisms (SNPs) in IGF1 pathway genes were genotyped in a case-control study consisting of 2070 stroke cases and 2243 controls. Main genetic effects and gene-gene interactive effects of the IGF1 pathway were evaluated. Weighted genetic risk scores (wGRS) were computed, and the associations between wGRS and gene expression were analysed. RESULTS: The variants at GHRH rs6032470 were significantly associated with high risk of hemorrhagic stroke (HS), and the adjusted OR (95%CI) was 1.368 (1.136-1.647). Significant additive interaction between rs6032470 and gender was detected for HS and ischemic stroke (IS). The association of rs6032470 and stroke was stronger in males than in females. Additionally, a significant gene-gene interaction of rs6032470-rs1874479 (IGFBP1) in relation to HS risk was identified (p < 0.05). IGF1 mRNA expression was significantly upregulated in IS, while it was linearly downregulated across rs6214 genotypes. In addition, IGFBP3 transcript variant 2 mRNA level was negatively correlated with wGRS (r = -0.285, p = 0.005). CONCLUSIONS: Our findings indicated that the IGF1 signalling pathway genes potentiated the risk of stroke through both main effects and gene-gene interactions. The genetic effect of GHRH rs6032470 on stroke was gender dependent. The wGRS of IGF1 pathway genes may be an independent predictor of stroke risk.

Association of Smoking-Related Knowledge, Attitude, and Practices (KAP) with Nutritional Status and Diet Quality: A Cross-Sectional Study in China.

BACKGROUND: Smoking is the second leading cause of death. Limited studies are available about smoking and overall diet quality. The current study was aimed at finding an association of s-KAP (smoking-related knowledge, attitude, and practices) with nutritional status and diet quality. METHODOLOGY: The current study was a cross-sectional community-based study conducted in Jurong city, China. Validated questionnaires were used for the collection of data regarding s-KAP and dietary intake. Correlation and multivariate linear regression analysis were used for the association of s-KAP scores with diet quality scores and nutritional status. RESULTS: The total numbers of participants were 7998 with a mean age of 59.3±11.4 years, including 38.5% males and 41.5% females. s-KAP scores were categorized into two groups, i.e., High s-KAP group and low s-KAP group. The High s-KAP group had significantly higher (P<0.05) diet scores and BMI but lower (P<0.05) WC (waist circumference) and WHR (waist to hip ratio) than the Low s-KAP group. Independent positive association (P<0.05) of s-KAP scores with diet scores was observed after the adjustment for age, gender, physical activity, alcohol consumptions, monthly income, and anthropometric measures (BMI, WC, and WHR). Similarly, smoking was positively associated (P<0.05) with diet scores after adjustment for covariates. CONCLUSION: In conclusion, the higher s-KAP scores indicated more knowledge regarding the harmful consequences of the smoking outcomes, positive attitude, less smoking practices, and having a good plan to quit smoking. Individuals with high s-KAP scores had good diet quality and lower adiposity measures. Furthermore, s-KAP scores and smoking status were having an independent positive association with diet scores.

Association of handgrip strength with the prevalence of hypertension in a Chinese Han population.

OBJECTIVE: Handgrip strength (HGS) exercise has been reported to reduce blood pressure in both hypertensive and normotensive patients. In this study, we evaluated the association of HGS with hypertension in a Chinese Han Population. METHODS: A total of 11,151 subjects mainly consisting of a rural population were recruited with a multi-stage sampling method in Jurong city, Jiangsu Province, China. Besides hypertension and diabetes, major chronic diseases were excluded. HGS was categorized into tertiles by age and gender. Logistic regression was used to estimate the association of HGS and hypertension with the odds ratio (OR) and 95% confidence interval (CI). RESULTS: From low to high tertiles of HGS, diastolic blood pressure (DBP) was significantly increased (74.52 ± 7.39, 74.70 ± 7.03, and 75.54 ± 7.01 mmHg, respectively; P trend = 0.001), as well as in females (P trend =0.003). The differences in DBP among the tertiles of HGS were still significant in females even after adjusting for covariates (P trend =0.048). No significant differences in systolic blood pressure (SBP) were observed among the tertiles of HGS (P>0.05). Compared to low HGS, high HGS was significantly associated with hypertension after adjustment for age and gender (adjusted OR, 1.19; 95% CI, 1.06-1.34; P =0.004). A stratified analysis showed that the significant association of high HGS and hypertension was also observed with the following factors even after adjusting for age and gender: female gender (adjusted OR, 1.25; 95% CI, 1.08-1.46; P=0.004), ages of 60-69 years (adjusted OR, 1.29; 95% CI, 1.06-1.57; P=0.011), and married (adjusted OR, 1.20; 95% CI, 1.06-1.37; P=0.005). However, no significant associations were found after adjusting for age, gender, smoking status, drinking status, body mass index, physical activity level, glucose, high- and low-density lipoprotein cholesterol, total cholesterol, and triglyceride (P>0.05). CONCLUSION: The findings of the current study suggest that HGS was positively correlated with DBP in a rural population, and high HGS was associated with hypertension in females; however, the association may be modified by smoking status, drinking status, body mass index, physical activity, cholesterol level, and glucose level. Further utilization of HGS exercises to intervene in the development and prognosis of hypertension should be verified in the future.

Comparison of the Correlates Between Body Mass Index, Waist Circumference, Waist-to-Height Ratio, and Chronic Kidney Disease in a Rural Chinese Adult Population.

OBJECTIVE: The aim of the article was to evaluate and compare the correlates of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with chronic kidney disease (CKD) among a rural Chinese adult population. DESIGN: This was a case-control study. METHODS: A total of 4,221 adults, aged 27 to 95 years, were divided into different groups based on the standard of CKD stages. A receiver operating characteristic curve was performed to evaluate and compare the predictive values of BMI, WC, and WHtR for CKD. Multiple logistic regression model and ordinal logistic regression model were used to estimate the association between BMI, WC, WHtR, and CKD. MAIN OUTCOME MEASURES: The main outcome variable was stage of CKD. RESULTS: The abnormality in BMI, WC, and WHtR was associated with the cumulative risk of CKD after adjusting for age, gender, smoking, and drinking, and corresponding odds ratios (ORs) (95% confidence intervals [CIs]) were 1.154 (1.009-1.319), 1.240 (1.077-1.428), and 1.191 (1.030-1.378). After further adjustment for blood lipid, hypertension, type 2 diabetes mellitus, and use of antihypertensive and antidiabetic agents, the association of WC and CKD remained statistically significant (adjusted OR = 1.220, 95% CI: 1.052-1.415). Both WC and WHtR were significantly associated with the risk of CKD in females, crude ORs (95% CIs) of cumulative effect of WC and WHtR with CKD were 1.534 (1.296-1.816) and 1.981 (1.683-2.331), respectively. The area under the curves of BMI, WC ,and WHtR for CKD Stage 3 were 0.531, 0.579, and 0.614, and pairwise comparisons showed the area under the curve of WHtR was significantly higher than BMI and WC (P < .001 and P = .002). CONCLUSION: Our findings suggested that abnormality in BMI, WC, and WHtR was associated with CKD in rural population, and WHtR was better in CKD prediction, especially in female.

Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence / Explorando a relação entre os níveis periféricos de bilirrubina total, glóbulos vermelhos e hemoglobina e a pressão arterial na infância e adolescência

Abstract Objective: Total bilirubin is beneficial for protecting cardiovascular diseases in adults. The authors aimed to investigate the association of total bilirubin, red blood cell, and hemoglobin levels with the prevalence of high blood pressure in children and adolescents. Methods: A total of 3776 students (aged from 6 to 16 years old) were examined using cluster sampling. Pre-high blood pressure and high blood pressure were respectively defined as the point of 90th and 95th percentiles based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Both systolic and diastolic blood pressure were standardized into z-scores. Results: Peripheral total bilirubin, red blood cell and hemoglobin levels were significantly correlated with age, and also varied with gender. Peripheral total bilirubin was negatively correlated with systolic blood pressure in 6- and 9-year-old boys, whilst positively correlated with diastolic blood pressure in the 12-year-old boys and 13- to 15-year-old girls (p < 0.05). Higher levels of red blood cell and hemoglobin were observed in pre-high blood pressure and high blood pressure students when compared with their normotensive peers (p < 0.01). The increases in red blood cell and hemoglobin were significantly associated with high blood pressure after adjusting for confounding factors. The ORs (95% CI) of each of the increases were 2.44 (1.52-3.92) and 1.04 (1.03-1.06), respectively. No statistical association between total bilirubin and high blood pressure was observed (p > 0.05). Conclusion: Total bilirubin could be weakly correlated with both systolic and diastolic blood pressure, as correlations varied with age and gender in children and adolescents; in turn, the increased levels of red blood cell and hemoglobin are proposed to be positively associated with the prevalence of high blood pressure.

Resumo Objetivo: A bilirrubina total é benéfica para proteger contra doenças cardiovasculares em adultos. Nosso objetivo foi investigar a associação dos níveis de bilirrubina total, glóbulos vermelhos e hemoglobina com a prevalência de pressão arterial elevada em crianças e adolescentes. Métodos: Um total de 3.776 estudantes (com idade entre 6-16 anos) foram examinados utilizando uma amostra em blocos. A pressão arterial elevada anterior e a pressão arterial elevada foram definidas como o 90° e 95° percentil, respectivamente, com base nos critérios do Quarto Relatório sobre Diagnóstico, Avaliação e Tratamento da Pressão Arterial elevada em Crianças e Adolescentes. A pressão arterial sistólica e pressão arterial diastólica foram padronizadas no escore z. Resultados: Os níveis periféricos de bilirrubina total, glóbulos vermelhos e hemoglobina foram significativamente correlacionados à idade, que também variou de acordo com o sexo. A bilirrubina total periférica apresentou uma correlação negativa com a pressão arterial sistólica em meninos com 6 e 9 anos, ao passo que apresentou uma correlação positiva com a pressão arterial diastólica em meninos de 12 anos e meninas de 13 a 15 anos (p < 0,05). Foram observados níveis mais elevados de glóbulos vermelhos e hemoglobina em estudantes com pressão arterial elevada anterior e pressão arterial elevada em comparação a indivíduos normotensos (p < 0,01). Os aumentos de glóbulos vermelhos e hemoglobina tiveram uma associação significativa com a pressão arterial elevada após ajuste dos fatores de confusão. As RC (IC de 95%) de cada um dos aumentos foram 2,44 (1,52-3,92) e 1,04 (1,03-1,06) respectivamente. Não foi observada nenhuma associação estatística entre o nível de bilirrubina total e a pressão arterial elevada (p > 0,05). Conclusão: A bilirrubina total pode ter correlações fracas com a pressão arterial sistólica e a pressão arterial diastólica, variando de acordo com a idade e o sexo em crianças e adolescentes, enquanto isso, propõe-se que o aumento dos níveis de glóbulos vermelhos e hemoglobina está positivamente associado à prevalência de pressão arterial elevada.

Common variants of ROCKs and the risk of hypertension, and stroke: Two case-control studies and a follow-up study in Chinese Han population.

The Rho kinases (ROCKs) are recognized as a critical regulator of vascular functions in cardiovascular disorders. It is crucial to illustrate the association of ROCKs genetic variation and hypertension and/or stroke events. Herein we aimed at investigating the association of ROCK1 and ROCK2 with hypertension and stroke in Chinese Han population. Seven tagSNPs at ROCK1 and ROCK2 were genotyped in a community-based case-control study consisting of 2012 hypertension cases and 2210 normotensive controls and 4128 subjects were further followed up. In stroke case-control study, 1471 ischemic stroke (IS) inpatients and 607 hemorrhagic stroke (HS) inpatients were collected, and 2443 age-matched controls were selected from the follow-up population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by logistic and Cox regression. The community-based case-control study didn't identify any significant tagSNPs associated with hypertension even after adjustment for covariates. The follow-up analysis showed that rs1481280 of ROCK1 significantly associated with incident hypertension (HR=1.130, P=0.048) after adjusting for covariates. rs7589629 and rs978906 of ROCK2 were significantly associated with incident IS (HR=1.373, P=0.004; HR=1.284, P=0.026) respectively. In stroke case-control study, rs288980, rs1481280 and rs7237677 were significantly associated with IS and the adjusted ORs (P values) of additive model were 0.879 (0.010), 0.895 (0.036) and 0.857 (0.002) respectively. Furthermore, rs288980, rs7237677 and rs978906 were significantly associated with HS and the adjusted ORs (P values) of additive model were 0.857 (0.025), 0.848 (0.018) and 0.856 (0.027) respectively. Our findings suggest that ROCK1 and ROCK2 contribute to the genetic susceptibility of hypertension and stroke.

Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence.

OBJECTIVE: Total bilirubin is beneficial for protecting cardiovascular diseases in adults. The authors aimed to investigate the association of total bilirubin, red blood cell, and hemoglobin levels with the prevalence of high blood pressure in children and adolescents. METHODS: A total of 3776 students (aged from 6 to 16 years old) were examined using cluster sampling. Pre-high blood pressure and high blood pressure were respectively defined as the point of 90th and 95th percentiles based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Both systolic and diastolic blood pressure were standardized into z-scores. RESULTS: Peripheral total bilirubin, red blood cell and hemoglobin levels were significantly correlated with age, and also varied with gender. Peripheral total bilirubin was negatively correlated with systolic blood pressure in 6- and 9-year-old boys, whilst positively correlated with diastolic blood pressure in the 12-year-old boys and 13- to 15-year-old girls (p<0.05). Higher levels of red blood cell and hemoglobin were observed in pre-high blood pressure and high blood pressure students when compared with their normotensive peers (p<0.01). The increases in red blood cell and hemoglobin were significantly associated with high blood pressure after adjusting for confounding factors. The ORs (95% CI) of each of the increases were 2.44 (1.52-3.92) and 1.04 (1.03-1.06), respectively. No statistical association between total bilirubin and high blood pressure was observed (p>0.05). CONCLUSION: Total bilirubin could be weakly correlated with both systolic and diastolic blood pressure, as correlations varied with age and gender in children and adolescents; in turn, the increased levels of red blood cell and hemoglobin are proposed to be positively associated with the prevalence of high blood pressure.

Evaluation of genetic effect of NOS3 and G×E interaction on the variability of serum bilirubin in a Han Chinese population.

Bilirubin was shown to be related to the generation and functional exertion of endothelial nitric oxide synthase (eNOS) whilst the genetic effect of NOS3 on bilirubin variability was rarely reported. Herein we assessed the associations of three single nucleotide polymorphisms (SNPs) of NOS3 (rs4496877, rs1808593, and rs3918186) with bilirubin elevation in 2077 adults. The results showed that rs1808593 was significantly associated with bilirubin elevation, and odds ratios (ORs) of dominant model for the elevation of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IDBIL) were 0.837, 0.821 and 0.754, respectively (P < 0.05 for all). Stratification analysis indicated that rs3918186 was significantly associated with the elevation of TBIL and IDBIL in the males, and ORs of dominant model were 1.505 and 1.440 with P < 0.05 for all. In the smoking group, significant associations of rs4496877, rs1808593, and rs3918186 with TBIL elevation were observed, and ORs of dominant model were 1.739, 0.758 and 1.626 (P < 0.05 for all). rs4496877 and rs3918186 were both associated with TBIL elevation in the drinking group, and ORs were 1.557 and 1.769 with P < 0.05 for all. In the ≥55 year-old group, rs4496877 and rs1808593 were significantly associated with DBIL and IDBIL elevations, and ORs were 1.340 and 0.790 (P < 0.05). Meanwhile, rs4496877, rs1808593, rs3918186, smoking, and drinking were shown to have a notable interaction effects on the TBIL elevation. Our findings supported that NOS3 harbors the genetic susceptibility to the bilirubin elevation. Age, gender, smoking, and drinking could be involved in the genetic modification of NOS3 on the bilirubin variability.