Zuoguang Wang

E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population

BackgroundGenetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension.MethodsHypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study.ResultsHypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C).ConclusionC602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.

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.

Association Study of the β2-Adrenergic Receptor Gene Polymorphisms and Hypertension in the Northern Han Chinese

Background The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population. Methodology/Principal Findings This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk. Conclusions/Significances We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.

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.

Alpha-adducin Gly460Trp polymorphism and hypertension risk: a meta-analysis of 22 studies including 14303 cases and 15961 controls.

Background No clear consensus has been reached on the alpha-adducin polymorphism (Gly460Trp) and essential hypertension risk. We performed a meta-analysis in an effort to systematically summarize the possible association. Methodology/Principal Findings Studies were identified by searching MEDLINE and EMBASE databases complemented with perusal of bibliographies of retrieved articles and correspondence with original authors. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. We selected 22 studies that met the inclusion criteria including a total of 14303 hypertensive patients and 15961 normotensive controls. Overall, the 460Trp allele showed no statistically significant association with hypertension risk compared to Gly460 allele (P = 0.69, OR = 1.02, 95% CI 0.94–1.10, Pheterogeneity<0.0001) in all subjects. Meta-analysis under other genetic contrasts still did not reveal any significant association in all subjects, Caucasians, East Asians and others. The results were similar but heterogeneity did not persist when sensitivity analyses were limited to these studies. Conclusions/Significance Our meta-analysis failed to provide evidence for the genetic association of α-adducin gene Gly460Trp polymorphism with hypertension. Further studies investigating the effect of genetic networks, environmental factors, individual biological characteristics and their mutual interactions are needed to elucidate the possible mechanism for hypertension in humans.

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.

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.