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ABSTRACT: Purpose: Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5'-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension. Materials and Methods: 472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5'-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted. Results: When comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, p<0.01). When subgrouped by gender, A frequency in NT group was still significantly higher than in EH group (male: OR= 4.264, CI 95%=2.780-6.543, p<0.01; female: OR=8.897, CI 95%=4.686-16.891, p<0.01), but not from PH group, either in male group or in female group. Ordinal Logistic Regression analysis showed that A>G variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, p<0.01). Conclusion: 5'-UCR -1248 A>G variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.
Yonsei medical journal 05/2013; 54(3):603-8. · 0.77 Impact Factor
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Hao Wang,
Jielin Liu,
Kuo Liu,
Ya Liu, Zuoguang Wang,
Yuqing Lou,
Qiuli Niu,
Wei Gu,
Lijuan Wang,
Mei Li,
Xiaoling Zhu,
Shaojun Wen
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ABSTRACT: The β1-adrenoceptor (ADRB1) gene Arg389Gly polymorphism has been extensively studied as a candidate gene in essential hypertension (EH), but no consensus has been reached on the relationship between this polymorphism and EH risk. To systematically explore their possible association, a meta-analysis was conducted. All relevant case-control trials in English-language publications before 1 June 2012 were identified by searching the PubMed and Embase databases. Finally, eight articles met our inclusion criteria, including a total of 5,088 patients with EH and 6,515 controls. No evidence of publication bias was found. Fixed-effects model and random-effects model were applied for dichotomous outcomes to combine results from individual studies. Overall, the Gly allelic frequency of Arg389Gly polymorphism was significantly lower in EH subjects than that in controls (Gly versus Arg: P = 0.04, OR = 0.89, 95 % CI [0.80-1.00], P heterogeneity = 0.03, I (2) = 52 %, random-effects model; GlyGly + ArgGly versus ArgArg: P = 0.02, OR = 0.86, 95 % CI [0.76-0.97], P heterogeneity = 0.08 and I (2) = 42 %, random-effect model). Subgroup analysis by ethnicity detected this association only in East Asians. In sensitivity analysis, the study by Bengtsson K was recognized as the main cause of heterogeneity, which was the only one study with the diagnostic standard for EH as systolic blood pressure (SBP) ≥160 mmHg or diastolic blood pressure (DBP) ≥90 mmHg. We concluded that the Gly allele of ADRB1 Arg389Gly polymorphism might confer lower risk for EH, especially in East Asians.
Molecular Biology Reports 04/2013; · 2.93 Impact Factor
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ABSTRACT: 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.Keywords: angiotensinogen; Chinese; meta-analysis; polymorphism
Hypertension Research 08/2011; 35(1):70-76. · 2.58 Impact Factor
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Yuqing Lou,
Jielin Liu,
Yao Li,
Ya Liu, Zuoguang Wang,
Kuo Liu,
Hai Wu,
Qiuli Niu,
Wei Gu,
Yanhong Guo,
Zhizhong Li,
Shaojun Wen
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ABSTRACT: 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.
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.
We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.
PLoS ONE 01/2011; 6(4):e18590. · 4.09 Impact Factor
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ABSTRACT: Numerous studies in Chinese populations have evaluated the association between the A-6G and A-20C polymorphisms in the promoter region of angiotensinogen gene and hypertension. However, the results remain conflicting. We carried out a meta-analysis for these associations.
Case-control studies in Chinese and English publications were identified by searching the MEDLINE, EMBASE, CNKI, Wanfang, CBM, and VIP databases. The random-effects model was applied for dichotomous outcomes to combine the results of the individual studies. We finally selected 24 studies containing 5932 hypertensive patients and 5231 normotensive controls. Overall, we found significant association between the A-6G polymorphism and the decreased risk of hypertension in the dominant genetic model (AA+AG vs. GG: P=0.001, OR=0.71, 95%CI 0.57-0.87, P(heterogeneity)=0.96). The A-20C polymorphism was significantly associated with the increased risk for hypertension in the allele comparison (C vs. A: P=0.03, OR=1.14, 95%CI 1.02-1.27, P(heterogeneity)=0.92) and recessive genetic model (CC vs. CA+AA: P=0.005, OR=1.71, 95%CI 1.18-2.48, P(heterogeneity)=0.99). In the subgroup analysis by ethnicity, significant association was also found among Han Chinese for both A-6G and A-20C polymorphisms. A borderline significantly decreased risk of hypertension between A-6G and Chinese Mongolian was seen in the allele comparison (A vs. G: P=0.05, OR=0.79, 95%CI 0.62-1.00, P(heterogeneity)=0.84).
Our meta-analysis indicated significant association between angiotensinogen promoter polymorphisms and hypertension in the Chinese populations, especially in Han Chinese.
PLoS ONE 01/2011; 6(12):e29489. · 4.09 Impact Factor
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ABSTRACT: 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 P(heterogeneity)=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 P(heterogeneity)=0.04) as well as in the homozygote comparison (P=0.006, OR=1.25, 95% CI=1.07-1.46 and P(heterogeneity)=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, P(heterogeneity)=0.08, recessive genetic model; P=0.009, OR=1.26, 95% CI=1.06-1.50, P(heterogeneity)=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.
Hypertension Research 01/2011; 34(3):389-99. · 2.58 Impact Factor
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ABSTRACT: Hyperplasia suppressor gene/mitofusion-2 (HSG/Mfn2) is a hyperplasia suppressor gene and an essential component of mitochondrial fusion machinery; however, the association between the single nucleotide polymorphism (SNP) of HSG/Mfn2 and hypertension is unclear.
In this study, 542 normotensive subjects (NT group) and 539 hypertensive patients (EH group) were screened for an association study between HSG/Mfn2 and hypertension.
The results showed that the genotype distribution and allelic frequency of rs873457, rs2336384, rs1474868, rs4846085 and rs2236055 were significantly different (p lt; 0.05 for all) between EH and NT groups, although those of rs4240897 and rs873458 were not. When comparing the dominant model, significant differences still existed (p lt; 0.05 for all). The allelic frequency of rs4240897 was also slightly different between EH and NT groups (P = 0.047). When subgrouped by sex, the genotype distribution and allelic frequency of all the SNPs (except rs873458) were significantly different in male (p lt; 0.05 for all) but not in female groups. For all the SNPs, only the allelic frequency of rs4240897 was obviously different in female NT and EH groups (p lt; 0.01). Logistic regression showed that body mass index and rs873457 were closely associated with BP after adjusting for age. The frequency of the C-G-A-A-A-C-C haplotype was significantly higher in essential hypertensive patients versus control individuals, both in the entire population, in male or female groups (p lt; 0.01 for all). As for other haplotypes, most were only significantly different in the entire population and male subjects.
The genetic variations of HSG/Mfn2 may be associated with hypertension in male Chinese.
Journal of atherosclerosis and thrombosis 10/2010; 18(1):24-31. · 2.69 Impact Factor
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ABSTRACT: 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.Keywords: adrenergic receptor; meta-analysis; polymorphism
Hypertension Research 08/2010; 33(11):1114-1123. · 2.58 Impact Factor
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ABSTRACT: Genetic 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.
Hypertensive 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.
Hypertensive 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).
C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.
BMC Medical Genetics 01/2010; 11:127. · 2.33 Impact Factor
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ABSTRACT: 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.
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, P(heterogeneity)<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.
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.
PLoS ONE 01/2010; 5(9). · 4.09 Impact Factor
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ABSTRACT: 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.
Clinical and Experimental Hypertension 06/2009; 31(4):316-29. · 1.07 Impact Factor
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ABSTRACT: A pilot study was conducted to investigate blood pressure level and vasoactive factors (VFs) among age- and sex-matched normotensive (NT), prehypertensive (PH), and hypertensive (EH) subjects. The results showed that angiotensin, arginine vasopressin, and endothelin were significantly higher, while adrenomedullin and calcitonin gene-related peptide were lower in the EH group than in the PH and NT groups. Nitric oxide synthase was not different among the three groups. There was a dose-response relationship between VFs and BP status. The results suggested that changes in blood VFs might be early warning signs of the development of prehypertension to hypertension, and important biomarkers for the early prevention of prehypertension.
Clinical and Experimental Hypertension 11/2008; 30(7):598-605. · 1.07 Impact Factor
