Shaojun Wen

Mitofusin-2 over-expresses and leads to dysregulation of cell cycle and cell invasion in lung adenocarcinoma

Abstract Mitofusin-2 (MFN2) is a mitochondrial protein associated with mitochondrial fusion process. It was initially identified as a hyperplasia suppressor and implicated in Charcot–Marie–Tooth disease. Recent studies showed that MFN2 played important roles in the development of multiple tumors. Here we examined MFN2 expression in 30 lung adenocarcinoma samples and revealed that the expression of MFN2 was significantly higher in lung adenocarcinoma tissues as compared to adjacent normal tissues. We then investigated the impact of MFN2 knockdown on A549 human lung adenocarcinoma cells and showed that cell proliferation, cell cycle and invasion behavior were all deregulated by MFN2 knockdown. And deregulation of cell cycle pathway after MFN2 knockdown was confirmed by microarray analysis. Furthermore, microarray analysis also revealed that different oncogenes such as RAP1A, RALB and ITGA2 were oppositely regulated by MFN2, which provided molecular clues for the paradoxical functions of MFN2 in tumor development. Taken together, our study unraveled the tumor-promoting functions of MFN2 in lung adenocarcinoma and implicated that the role of MFN2 in cancer development might be more complicated than expected and should be explored in detail in the future.

A46G and C79G polymorphisms in the β2-adrenergic receptor gene ( ADRB2 ) and essential hypertension risk: a meta-analysis

No consensus has been reached on the association between the β2-adrenergic receptor polymorphisms A46G and C79G and essential hypertension risk. We performed a meta-analysis to confirm the possible association. After reviewing 303 reports in PubMed and 359 reports in Embase, we included in our meta-analysis 18 articles (20 studies) that met our inclusion criteria. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. There was no statistical association between A46G and hypertension risk in all subjects, Asians or Caucasians. However, an association was observed in the dominant genetic model (AA vs. (AG+GG)) (P=0.04, odds ratio (OR)=1.38, 95% confidence interval (CI) 1.01–1.87, Pheterogeneity=0.98, fixed-effects model) in the subgroup of mixed Africans. No overall statistical association could be found between C79G and hypertension risk or any ethnic subgroup. In the research conducted on severe hypertension (systolic blood pressure ⩾160 mm Hg and/or diastolic blood pressure ⩾95 mm Hg hypertensive population), significant association was found in the dominant genetic model (CC vs. (CG+GG)) (P=0.04, OR=1.38, 95% CI 1.02–1.86, Pheterogeneity=0.03, random-effects model), and there was also a borderline significance between the C79 allele and severe hypertension (P=0.05, OR=1.26, 95% CI 1.00–1.57, Pheterogeneity=0.04, random-effects model). No association could be found in this study between the two polymorphisms and stage 2 hypertension. More studies stratified for different ethnicities and different stages of hypertension should be performed in the future.

α-adducin Gly460Trp polymorphism and essential hypertension risk in Chinese: a meta-analysis

No clear consensus has been reached on the α-adducin polymorphism (Gly460Trp) and essential hypertension (EH) risk in Chinese. We conducted a meta-analysis in an effort to systematically explore the possible association. Case-control studies in Chinese and English performed with human subjects were identified by searching the MEDLINE, EMBASE, China Biological Medicine Database, China National Knowledge Infrastructure platform, Wanfang and VIP databases. The fixed-effects model and the random-effects model for dichotomous outcomes were applied to combine the results of the individual studies. We selected 20 studies that met the inclusion criteria, including a total of 5562 patients with hypertension and 4289 controls. Overall, our findings supported the hypothesis that the ADD1 Gly460Trp polymorphism is associated with EH in the Chinese population. A borderline association was found between the tryptophan (Trp) allele of the Gly460Trp variant and hypertension (P=0.05, Odds ratio (OR)=1.08, 95% confidence interval (CI)=1.00–1.17 and Pheterogeneity=0.02). Significantly increased risk was observed in the recessive genetic model (P=0.0009, OR=1.24, 95% CI=1.09–1.41 and Pheterogeneity=0.04) as well as in the homozygote comparison (P=0.006, OR=1.25, 95% CI=1.07–1.46 and Pheterogeneity=0.03). Furthermore, in the subgroup analysis, our results support a positive association among Chinese Han individuals (P=0.001, OR=1.25, 95% CI=1.09–1.42, Pheterogeneity=0.08, recessive genetic model; P=0.009, OR=1.26, 95% CI=1.06–1.50, Pheterogeneity=0.03, homozygote comparison). No apparent association was identified in Kazakhs. Our meta-analysis suggests that the Gly460Trp polymorphism might increase the risk of hypertension in Chinese populations, especially in Han Chinese. Further studies investigating gene–gene, gene–environment and mutual interactions are needed to better understand the role of ADD1 in hypertension.

The association between endothelial nitric oxide synthase gene G894T polymorphism and hypertension in Han Chinese: a case-control study and an updated meta-analysis

Abstract Background: The G894T (rs1799983) polymorphism in endothelial nitric oxide synthase (eNOS/NOS3) gene has been implicated in susceptibility to essential hypertension (EH) in some studies, but no clear consensus has been reached in the Chinese population. Aims: This study aimed to investigate the association of the G894T polymorphism and EH in Han Chinese. Subjects and methods: First, a case-control study was performed involving 1525 subjects in northern Han Chinese to study the association between G894T variants and EH and then a meta-analysis was conducted of all available studies in Han Chinese. A total of 25 studies comprising 13 443 subjects were finally included in this meta-analysis. Results: The present case-control study failed to show significant association of G894T variant with EH in northern Han Chinese. The subsequent meta-analysis showed that this polymorphism might be associated with EH in Han Chinese (p < 0.001, OR = 1.32), especially in southern Han Chinese (p < 0.001, OR = 1.59), but not in northern Han Chinese (p = 0.12, OR = 1.16). The meta-regression analysis suggested that the geographic difference of subjects was related to heterogeneity (p = 0.029). Conclusions: The relationship between the G894T polymorphism and hypertension in Han Chinese may be attributed to the difference in geographic background of subjects. It is necessary to carry out further research with a large sample size and focusing on gene–environment interactions.

Association between single-nucleotide polymorphisms in six hypertensive candidate genes and hypertension among northern Han Chinese individuals

Hypertension is one of the leading risk factors for mortality. The renin–angiotensin–aldosterone system (RAAS) is a potent and powerful mediator in the homeostasis of hypertension. Here, the association between six candidate genes, renin, adrenoceptor β3, angiotensinogen, aldosterone synthase, angiotensin II receptor type 1 and angiotensin II receptor type 2, that are related to RAAS and essential hypertension (EH) was evaluated and explored in northern Chinese Han individuals. A case–control study including 1090 EH cases and 700 controls was performed. Eight single-nucleotide polymorphisms (SNPs), rs699, rs4762, rs5707, rs5186, rs4994, rs1799998, rs5193 and rs5194, located in the six genes were genotyped with TaqMan real-time PCR method. Statistical analysis software (SPSS 17.0) was used for descriptive statistics and association analyses. Among the six genes related to RAAS, the frequencies of rs4994 (ADRB3) and rs5194 (AGTR2) were found to be significantly different between the EH cases and controls (P<0.05). Logistic regression analyses adjusted for covariates showed rs4994 to be closely associated with EH under the recessive (P=0.019, odds ratio (OR)=0.373, 95% confidence interval (CI) 0.163–0.851) and homozygous (P=0.028, OR=0.394, 95% CI 0.172–0.903) models. The association was also significantly close in the male subset (P<0.05). Significant association was also observed between rs1799998 (CYP11B2) and EH (P<0.05) in the dominant, additive and allelic models. These data demonstrated that ADRB3 rs4994 and CYP11B2 rs1799998 were significantly closely associated with EH in northern Han Chinese individuals. The CC of rs4994 and CC or C allele of rs1799998 might be protective genetic factors of hypertension.

Association between the angiotensinogen gene T174M polymorphism and hypertension risk in the Chinese population: a meta-analysis.

No consensus has been reached on the association between the angiotensinogen gene polymorphism T174M and hypertension risk in the Chinese population. We conducted a meta-analysis to systematically pursue their possible association. Case–control studies in the Chinese and English publications were identified by searching the MEDLINE, EMBASE, CBM, CNKI, Wanfang and VIP databases. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. After this, we selected 16 studies that met the inclusion criteria. In total, the selected studies contributed a study population containing 3828 hypertensive patients and 3251 normotensive controls. We found no statistical association between the T174M polymorphism and hypertension risk in all subjects, in a Han Chinese subgroup or in non-Han Chinese minorities. However, a statistically significant association was observed between the T174M polymorphism and a hypertensive group (systolic blood pressure ⩾160 mm Hg and/or diastolic blood pressure ⩾95 mm Hg) in the dominant genetic model (MM+MT vs. TT: P=0.03, odds ratio=1.71, 95% confidence interval 1.07–2.74, Pheterogeneity=0.27, I2=24%, fixed-effects model). No evidence of publication bias was observed. More studies, especially studies stratified for different stages of hypertension, should be performed in the future to fully examine this question. Studies investigating gene–gene interactions, gene—environment interactions, as well as their mutual interactions will also be important.

Renal Denervation vs Pharmacotherapy for Resistant Hypertension: A Meta-Analysis.

The effect of renal denervation (RD) for resistant hypertension remains controversial because of the conflicting results of finished and ongoing studies. The authors performed a meta‐analysis of case‐control studies to identify whether renal sympathetic denervation or pharmacotherapy (PHAR) was more effective for resistant hypertension. A systematic Internet database search of relevant papers written in English was performed. A total of nine studies met the inclusion criteria, with a total of 1096 patients. When comparing the RD group with the PHAR group, there was a significant decrease in systolic blood pressure (SBP) (weighted mean difference, −12.81 mm Hg; 95% confidence interval [CI], −22.77 mm Hg to −2.85 mm Hg; P=.01) and diastolic blood pressure (DBP) (weighted mean difference, −5.56; 95% CI, −8.15 mm Hg to −2.97 mm Hg; P<.0001). This pooled analysis shows that for patients with resistant hypertension, RD is more effective in reducing SBP and DBP than PHAR. RD may be more effective in special subgroups of patients, which needs to be identified in future investigations.

G-protein beta 3 subunit polymorphisms and essential hypertension： a case-control association study in northern Han Chinese

Objective To explore the association between the three polymorphisms [ C825T, C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recruited 731 hypertensive patients and 673 control subjects (the calculated power value was > 0.8). Genotyping was performed to identify C825T, C1429T and G(-350)A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models (additive, dominant and recessive models). Results The genotype distribution and allele frequencies of C825T, C1429T and G(-350)A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C1429T and G(-350)A polymorphisms and the risk of essential hypertension in any genetic model. Linkage disequilibrium was only detected between C825T and C1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C1429T and G(-350)A] were not significantly associated with essential hypertension in northern Han Chinese population.

The association between the polymorphisms in a sodium channel gene SCN7A and essential hypertension: a case-control study in the Northern Han Chinese.

Nax, an α‐subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Nax/SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case‐control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033–1.592]; P = 0.013, OR = 1.203, 95%CI [1.040–1.392]; respectively). The three SNPs were in close pair‐wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G–A–T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G–A–T will be a genetic risk factor for EH in the Northern Han Chinese population.

Is prehypertension really different from normotension and hypertension? A case-control pilot proteomic study in Chinese.

This study was designed to investigate the differences in the plasma proteome of healthy normotensive, prehypertensive, and hypertensive subjects. A case-control pilot study was conducted among well-matched subjects. Plasma protein was analyzed by two-dimensional electrophoresis combined with MALDI-TOF mass spectrometry. The results showed that there were 22 differentially expressed spots among the three groups, which corresponded to 18 proteins involved in inflammation and immunity, lipid metabolism, transport, coagulation and fibrinolysis, cell proliferation and apoptosis, and anti-oxidation. With an increase in blood pressure, these proteins were differentially expressed which indicated that prehypertension probably was an early stage of hypertension.