Changyi Wang

Plasma miR-126 Is a Potential Biomarker for Early Prediction of Type 2 Diabetes Mellitus in Susceptible Individuals

Type 2 diabetes mellitus (T2DM) is a major public health problem in China. Diagnostic markers are urgently needed to identify individuals at risk of developing T2DM and encourage them to adapt to a healthier life style. Circulating miRNAs present important sources of noninvasive biomarkers of various diseases. Recently, a novel plasma microRNA signature was identified in T2DM. Here, we evaluated the T2DM-related miRNA signature in plasma of three study groups: normal (fasting glucose (FG), 4.8–5.2 mmol/L), T2DM-susceptible (FG, 6.1–6.9 mmol/L), and T2DM individuals (FG, ≥7.0 mmol/L) and tested the feasibility of using circulating miRNAs to identify individuals at risk of developing T2DM. Among the 5 miRNAs included in the signature, miR-29b and miR-28-3p are not detectable. miR-15a and miR-223 have comparable expression levels among three groups. Notably, miR-126 is the only miRNA that showed significantly reduced expression in susceptible individuals and T2DM patients compared to normal individuals, suggesting that miR-126 in circulation may serve as a potential biomarker for early identification of susceptible individuals to T2DM.

Polymorphism −116C/G of Human X-box-Binding Protein 1 Promoter is Associated with Risk of Alzheimer's Disease

Alzheimers disease (AD) is a multifactor disease that has been reported to have a close association with endoplasmic reticulum (ER) stress response. In the response, the regulator factor human X‐box‐binding protein 1 (XBP1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid‐beta (Aβ) and tau, and play an important role in the survival of neurons. The aim in the study was to analyze the potential association between the −116C/G polymorphism of XBP1 and the risk of AD.

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients A Population-Based, Prospective Cohort Study

Background and Purpose— Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries. Methods— A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation. Results— After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65–2.89), 2.40 (1.56–3.67), and 2.73 (1.83–4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (<15 &mgr;mol/L), the hazard ratios (95% confidence intervals) for IS in the highest tHcy category (≥30 &mgr;mol/L) were 4.96 (3.03–8.12), 6.11 (3.44–10.85), and 1.84 (0.52–6.46) in the total, males, and females participants, respectively. However, we did not observe a significant relationship between tHcy and the risk of coronary heart disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 &mgr;mol/L (27.92%) in patients with essential hypertension. Conclusions— Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels.

Elevated plasma homocysteine level is associated with ischemic stroke in Chinese hypertensive patients

BACKGROUND Accumulating data suggest that hyperhomocysteinemia is associated with the risk of ischemic stroke (IS) and coronary heart disease (CHD) in the general population, but the relationship remains unclear in hypertensive patients. We examined the association of total homocysteine (tHcy) with IS and CHD in hypertensive patients. METHODS A total of 5935 Chinese hypertensive patients were recruited in a community-based cross-sectional study from 60 communities in Shenzhen, China. Plasma tHcy was quantitatively measured using the enzyme cycle method. Conventional risk factors for IS and CHD were obtained through questionnaire interviews and physical examinations. We included cerebral infarction, embolism and small-vessel disease as IS; and myocardial infarction, angina pectoris, coronary revascularization, and cardiac arrest as CHD. IS and CHD were retrospectively adjudicated by specialists via interviews, hospital records or relevant tests. RESULTS Significantly higher values of tHcy were observed in IS patients than in non-IS controls among both men and women. Greater tHcy level was dose dependently associated with an increased risk of IS presence in women, men and them combined (p-trend: 0.002, 3.8×10(-4) and 0.001). The odds ratios (95% CI) of IS for tHcy ≥30 (vs. <15) μmol/L were 2.84 (1.73-4.34) in men, 4.41 (1.62-9.15) in women, and 2.86 (1.72-4.75) in their combination after adjusting for other main risk factors of IS. We did not find any significant association between tHcy and presence of CHD after the adjustment for covariates. CONCLUSIONS Plasma homocysteine level is positively associated with the presence of IS, but not CHD, in Chinese hypertensive patients.

The interactions between alcohol consumption and DNA methylation of the ADD1 gene promoter modulate essential hypertension susceptibility in a population-based, case-control study.

The potential effects of the interactions between DNA methylation (CpG1 and CpG2-5 methylation levels) of the α-adducin (ADD1) gene promoter and ADD1 tagSNPs (tag single-nucleotide polymorphisms) or the environmental factors on essential hypertension (EH) risk have not been clarified. Thus, we performed an age- and gender-matched case–control study to investigate the association between ADD1 tagSNPs and EH. A total of 1020 subjects with EH and 1020 normotensive subjects were genotyped by melting temperature shift technology. Logistic regression was used to assess the associations of ADD1 tagSNPs, environmental factors and EH. The generalized multifactor dimensionality reduction (GMDR) method was applied to explore the potential interactions. Under additive, dominant and recessive models, no significant associations were evidenced between EH and rs3755885, rs2071694, rs4963 or rs3775067 with the complete data set or the gender-stratified analysis after adjusting for triglycerides, body mass index and alcohol consumption. However, we observed a significant association between rs4961 and EH under the dominant model after Bonferroni correction when adjusting for confounding factors in the entire sample (odds ratio (OR)=0.64, 95% confidence interval (CI)=0.50–0.83, P=0.001). In GMDR, the two-factor interaction model of alcohol consumption and DNA methylation (CpG1 methylation) was the best model, with a maximum cross-validation consistency of 9/10 and testing balance accuracy of 0.63 (P=0.01). Our results indicate that the SNP rs4961 has a protective role in the development of EH. In conclusion, the interactions between alcohol consumption and DNA methylation (CpG1 methylation) of the ADD1 gene promoter have a significant role in modifying EH susceptibility.

Vascular Endothelial Growth Factor Gene Promoter Polymorphisms and Alzheimer's Disease Risk: A Meta‐Analysis

Conclusions on the association between polymorphisms in the vascular endothelial growth factor (VEGF) gene promoter and risk of Alzheimers disease (AD) are ambiguous, and sufficient evaluation of the association is lacking. Therefore, we performed a meta‐analysis of observational studies to explore the association between polymorphisms in the VEGF gene promoter and AD risk.

Association between homocysteine and incidence of ischemic stroke in subjects with essential hypertension: a matched case-control study.

Abstract Background: To assess the association between total plasma homocysteine (tHcy) and ischemic stroke (IS) in hypertensive subjects in a matched case-control study. Methods: This is a 1:2 matched and population-based case-control study, all of the participants were recruited from the 60 communities in Shenzhen, China. Demographic and socioeconomic characteristics, medical records, lifestyle risk factors and other clinical characteristics were obtained from all of the subjects. The association between tHcy and incidence of IS was analyzed by using conditional logistic regression models. Results: The median values of plasma tHcy were significantly higher in IS subjects than in non-IS subjects, especially in women. After adjusted for the confounding factors in Model 2, compared with the lowest quartile of tHcy, the odds ratios (ORs) and 95% CIs of the highest quartile of tHcy for IS were 0.83 (0.36–1.90) in men, 4.51 (1.29–15.7) in women and 1.31 (0.70–2.47) in the total subjects; the ORs and 95% CIs for IS per 5 μmol/L increase in homocysteine were 1.11 (0.99–1.22), 1.25 (1.03–1.58) and 1.15 (1.01–1.28) in men, women and total subjects, respectively. We observed significant associations in crude model, Model 1 and Model 2 in women for the comparison of tHcy ≥ 15 μmol/L versus < 15 μmol/L. Interaction analysis showed that the association of tHcy with IS was significant in women (p-interaction = 0.04). Conclusion: This matched case-control study indicates that tHcy may increase the susceptibility to IS in essential hypertension subjects, especially in women. Further large prospective cohort studies are needed to confirm our findings.

Association between Polymorphisms of the AKT1 Gene Promoter and Risk of the Alzheimer's Disease in a Chinese Han Population with Type 2 Diabetes

Alzheimers disease (AD) is a multifactor disease that has been reported to have a close association with type 2 diabetes (T2D) where the v‐akt murine thymoma viral oncogene homolog 1 (AKT1) plays an important role in the protein synthesis pathways and cell apoptosis processes. Evidence has been shown that AKT1 protein may be related to AD risk among patients with T2D. The aim of this study was to analyze the potential association between single nucleotide polymorphisms of AKT1 promoter and the risk of AD among patients with T2D.

Association Between Promoter Polymorphisms of the GRP78 Gene and Risk of Type 2 Diabetes in a Chinese Han Population

There are large amounts of unfolding or misfolding protein accumulation in the endoplasmic reticulum in patients with type 2 diabetes (T2D), which in turn induces the expression of the glucose-regulated protein 78 (GRP78) that plays a key role in influencing insulin secretion and maintaining glucose homeostasis in pancreatic beta cells. The aim in the study is to analyze the potential association between single-nucleotide polymorphisms (SNPs) of GRP78 and the risk of T2D. To assess the association between GRP78 polymorphisms and T2D, a case-control study was conducted among 1058 consecutive unrelated subjects. Of the 1058 subjects, 523 of them were diagnosed with T2D and 535 of them were healthy controls. Four SNPs with R(2)>0.8 and the minor allele frequency>0.05 (rs391957, rs17840761, rs17840762, and rs11355458) in the GRP78 gene promoter were analyzed. Overall, no associations of GRP78 polymorphisms with T2D were observed in genotypic analyses. In addition, haplotypes combining those SNPs in the promoter in high linkage disequilibrium were also not associated with a T2D risk. However, the levels of fasting plasma glucose and HbA1c in patients with the -415AA/-180GG genotype were significantly lower than those of the patients with -415GG/-180deldel and -415AG/-180Gdel genotypes, and the level of fasting insulin in patients with the -415AA/-180GG genotype was significantly lower than that of the patients with -415GG/-180deldel. The study does not support a role for promoter polymorphisms of GRP78 in T2D in a Chinese Han population, but it does provide a clue for association between low levels of fasting plasma glucose, HbA1c and fasting insulin, and the -415AA/-180GG model.

The nitric oxide synthase 3 G894T polymorphism associated with Alzheimer's disease risk: a meta-analysis.

The association between the G894T polymorphism (Glu298Asp) of nitric oxide synthase 3 (NOS3) and risk of Alzheimer’s disease (AD) was explored by performing a meta-analysis of case-control studies. Bibliographical searches were conducted in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Two investigators independently assessed abstracts for relevant studies, and reviewed all eligible studies. We adopted regrouping in accordance with the most probably appropriate genetic model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association. We performed a meta-analysis including 21 published articles with 23 case-control studies (5,670 cases and 5,046 controls). In the analyses, we found significant association between G894T polymorphism and AD risk under a complete overdominant model (GG + TT vs. GT) (OR = 1.18; 95%CI, 1.04–1.35; P = 0.010). When stratified by time of AD onset, we found the association between this polymorphism and AD susceptibility to be more substantial among late onset patients than among early onset patients (OR for late vs. early onset: 1.33 vs. 1.02, P interaction = 0.049). The meta-analysis showed that the polymorphism G894T of NOS3 was associated with risk of AD.