Yuqing Lou

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.

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.

A-6G and A-20C polymorphisms in the angiotensinogen promoter and hypertension risk in Chinese: a meta-analysis.

Background 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. Methods and Results 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, Pheterogeneity = 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, Pheterogeneity = 0.92) and recessive genetic model (CC vs. CA+AA: P = 0.005, OR = 1.71, 95%CI 1.18–2.48, Pheterogeneity = 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, Pheterogeneity = 0.84). Conclusion Our meta-analysis indicated significant association between angiotensinogen promoter polymorphisms and hypertension in the Chinese populations, especially in Han Chinese.