Interaction between gene polymorphisms in MLL3 gene and TGF-β signal pathway with the susceptibility of type B aortic dissection in the Chinese population

Objective: To investigate the impact of MLL3 polymorphisms and Transforming growth factor-β (TGF-β) pathway additional their interactions with type B aortic dissection (AD) risk based on the Chinese population. Methods: We investigated the MLL3 (rs10244604, rs6963460, rs1137721), TGFβ1 (rs1800469), TGFβ2 (rs900), TGFR1 (rs1626340) and TGFR2 (rs4522809) gene polymorphisms analysis. Logistic regression was performed to investigate the association between 7 SNPs and Type B AD. GMDR software was used to analyze gene-gene and gene-environment interactions. Odds ratio (OR) with a 95% confidence interval (CI) was employed to evaluate the association of genes and Type B AD risk. Results: Genotypes and alleles distribution in case and control groups showed significant differences (P<0.05). Logistic regression has shown that the Type B AD risk was the highest in those with rs1137721 CT genotype, (OR=4.33, 95%CI=1.51-12.40). Meanwhile, WBC, Drinking, Hypertension, TG, and LDL-C were independent risk factors for Type B AD. Respectively, Logistic regression showed that the Type B AD risk was the highest in those with rs1137721-TT+CT and rs4522809-AA genotype (OR=6.72, 95% CI=1.56-29.84), and was lowest in those with rs1137721-CC and rs4522809-AA+GG genotype (OR=4.38, 95%CI=0.92-20.83). However, 55-month median long-term follow-up were not show significant.Conclusion: MLL3 (rs1137721) with TGFβ1 (rs4522809) polymorphisms may be closely related to the development of Type B AD. Inflammation reaction and lipid metabolism were associated with the morbility of Type B AD. Moreover, there exist gene-gene interactions among these susceptibility genes. These may become new diagnostic and research goal for Type B AD.

Usefulness of estimated pulse wave velocity for identifying prevalent coronary heart disease: findings from a general Chinese population

Background Aortic stiffness and coronary heart disease (CHD) share a similar spectrum of risk factors; previous studies have identified the association between aortic stiffness and CHD. Recent studies have demonstrated estimated pulse wave velocity (ePWV) as a simple and easy-acquired indicator of aortic stiffness. Our work aims to evaluate the association between ePWV and the prevalence of CHD and assess the value of ePWV for the identification of prevalent CHD. Methods The current cross-sectional work included 7012 subjects from rural areas of southeastern China between September 2020 and February 2021. ePWV was calculated from age and mean blood pressure by specific algorithm. Results The prevalence of CHD in our population was 3.58% (251 patients among 7012 subjects). After adjusting for age, sex, education, income and exercise level, current smoking and drinking status, body mass index, waist circumference, fasting plasma glucose, total cholesterol, high density lipoprotein, estimated glomerular filtration rate and cerebrovascular diseases, each standard deviation increment of ePWV would produce an additional 37.8% risk of prevalent CHD. Moreover, after dividing ePWV into quartiles, the 4th quartile of ePWV showed a significant risk of prevalent CHD (OR (95% CI): 3.567 (1.963–6.479)) when compared with the 1st quartile. Additionally, the subgroup analysis showed the association between ePWV and prevalent CHD was robust to several common risk factors of CHD, including age, sex, body mass index, hypertension, diabetes and reduced estimated glomerular filtration rate. Finally, the area under curve (AUC) displayed an improvement when adding ePWV into common CHD risk factors (0.705 vs. 0.718. P = 0.044). Consistently, net reclassification index (0.436, 95% CI: 0.301–0.571, P < 0.001) and integrated discrimination index (0.004, 95% CI: 0.001–0.006, P = 0.002) demonstrated the value of ePWV to optimize the identification of prevalent CHD in the general population. Conclusion The present analysis implicates the robust association between ePWV, a simple, rapid, and practical marker of aortic stiffness, and prevalent CHD in the general Chinese population. More importantly, the results suggest the value of ePWV as a potential marker to improve the identification of prevalent CHD.

Association Between Sensory Loss and Falls Among Middle-Aged and Older Chinese Population: Cross-Sectional and Longitudinal Analyses

Introduction: Previous studies have suggested that sensory loss is linked to falls. However, most of these studies were cross-sectional designed, focused on single sensory loss, and were conducted in developed countries with mixed results. The current study aims to investigate the longitudinal relationship between hearing loss (HL), vision loss (VL) and dual sensory loss (DSL) with falls among middle-aged and older Chinese population over 7 years.Methods: The data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 7,623 Chinese older adults aged over 45 were included at baseline 2011 in this study. Self-reported falls and HL/VL/DSL were accepted. Other confounding variables included age, sex, BMI, educational level, marital status, various physical disorders and lifestyles. The impact of baseline sensory status on baseline prevalence of falls and incident falls over 7 years were assessed using logistic regression analyses. A logistic mixed model was used to assess the association between time-varying sensory loss with incident falls over 7 years after adjusted with multi-confounding factors.Results: Single and dual sensory loss groups had significantly higher prevalence of falls compared to no sensory loss (NSL) group (DSL: 22.4%, HL: 17.4%, VL: 15.7%, NSL: 12.3%). Baseline HL (OR: 1.503, 95% CI: 1.240–1.820), VL (OR: 1.330, 95% CI: 1.075–1.646) and DSL (OR: 2.061, 95% CI: 1.768–2.404) were significantly associated with prevalence of falls. For longitudinal observation over 7 years, baseline HL/DSL and persistence of all types of sensory loss were associated with incidence of falls. Time-varying HL (OR: 1.203, 95% CI: 1.070–1.354) and DSL (OR: 1.479, 95% CI: 1.343–1.629) were associated with incident falls after adjusted with multi-confounders, while VL was not.Conclusion: HL and DSL are significantly associated with both onset and increased incidence of falls over 7 year's observation in middle-aged and elderly Chinese population. Persistence or amelioration of sensory loss status could exert divergent influences on incidence of falls, which should be considered in the development of falls-prevention public health policies for aging population.

SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population

Objectives A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. Methods The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. Result For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16–1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. Conclusions SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

Association of dietary patterns with obesity and metabolically healthy obesity phenotype in Chinese population: a cross-sectional analysis of China Multi-Ethnic Cohort Study

Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favorably associated with obesity and MHO phenotype in a Chinese Multi-Ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort (CMEC) study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11.2% were with obesity. MHO phenotype was present in 5.7% of total population and 52.7% of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23% decreased odds of obesity (OR = 0.77, 95% CI: 0.71-0.83, Ptrend <0.001), and 27% increased odds of MHO (OR = 1.27, 95% CI: 1.10-1.48, Ptrend =0.001) in population with obesity. However, aMED diet showed no obvious favorable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.

MRNA Profiling Involved in Triggering of STAT1 with Regulatory Involvement of IRF7, PTPRF, and miR-145p in Patients Suffering from Gall Bladder Carcinoma

Background. Gall Bladder Cancer (GBC) is a type of extremely malignant tumor, which has high incidences of mortality. There is rare information about its mechanisms of invasion and gene expression regulations. microRNA-155 (miR-155) has mostly been reported to be over expressed in cases of solid tumors and hematopoietic malignancies. In this study, we have investigated the role and clinical significance of miR-155 in a Chinese population suffering from GBC and compared the results with nonneoplastic inflammation. Methods. Tissue specimens were collected on 50 patients of Gall Bladder Carcinoma and 10 patients suffering from nonneoplastic inflammation who have undergone surgeries at the Department of Pathology, Renji Hospital, Shanghai, from January 2019 to January 2020. We performed profiling of miR-155 expression in both nonneoplastic and gall bladder carcinoma tissues by QRT-PCR. Results. Expression levels of miR-155 were found to be extremely high in GBC patients in comparison to the nonneoplastic tissues ( ∗ P < 0.05 ), as high miRNA is correlated with TNM stages. Further results noted were that miR-145-5p expressed genes mimic the gene expression of STAT1, a downregulation of IRF7 was noted in the GBC, and an activation of STAT1 was significantly noted in carcinoma cells of the gallbladder. Downregulation of PTPRF was also noted during the expression of miR-145. Conclusions. As downregulation of IRF7 is linked with low rates of survival, it was found that gall bladder carcinoma patients may face high mortality. The STAT-1 expression of unregulated in GBC patients was also noted.