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

Abstract

No consensus has been reached on the association between the b2-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)) (P¼0.04, odds ratio (OR)¼1.38, 95% confidence interval (CI) 1.01-1.87, P heterogeneity ¼0.98, 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 X160 mm Hg and/or diastolic blood pressure X95 mm Hg hypertensive population), significant association was found in the dominant genetic model (CC vs. (CG+GG)) (P¼0.04, OR¼1.38, 95% CI 1.02-1.86, P heterogeneity ¼0.03, random-effects model), and there was also a borderline significance between the C79 allele and severe hypertension (P¼0.05, OR¼1.26, 95% CI 1.00-1.57, P heterogeneity ¼0.04, 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.

Reevaluation of the association of seven candidate genes with blood pressure and hypertension: a replication study and meta-analysis with a larger sample size

“…17,18 Upon examining the association results separately by panel, we found that the direction and strength of the associations with BP traits were almost concordant for the two SNPs; that is, CYP11B2 rs1799998 and AGT rs699 (Supplementary Table 1). In addition, we found significant associations of ADRB2 rs1042713 and ACE rs4341 with SBP (P ¼ 0.004 for rs4341), DBP (P ¼ 0.005 for rs1042713 and P ¼ 0.0118 for rs4341), and/or hypertension (P ¼ 0.008 for rs1042713 and P ¼ 0.002 for rs4341) in the CAGE study panel 3, in directions that were consistent with those of previous studies; 16,27,28 however, these associations were not replicable in panel 1 and panel 2 (Supplementary Table 1). …”

“…[14][15][16][17][18][19][20] Compared with Japanese samples genotyped in this study, the relative increase in joint meta-analysis samples appeared to be modest (that is, 5-40%) at all loci except AGT rs699 for SBP/DBP association, whereas this increase was prominent (that is, 105-586%) for hypertension association, thereby providing the joint meta-analysis, in particular, for case-control study (5757-17399 cases vs. 11240-23338 controls) with reasonable power. For SBP and DBP, there were significant associations (two-tailed Po0.012, putative risk-allele homozygote vs. non-risk-allele homozygote) with AGT rs699 (P ¼ 0.001 for SBP), CYP11B2 rs1799998 (P ¼ 2.0 Â 10 À6 for SBP; P ¼ 3.1 Â 10 À6 for DBP), and ACE rs4340 (P ¼ 0.01 for DBP) (Supplementary Table 2).…”

“…With the exception of four variants (which were on the HumanHap550 BeadArray) in panel 1, samples were genotyped using the TaqMan assay for eight SNPs from seven unique candidate genes (Table 2). [14][15][16][17][18][19][20] These genes included AGT (rs699, M235T), Genetic association with hypertension F Takeuchi et al…”

“…The individual contribution of each of these genes to BP variation and/or hypertension in the general population has not been thoroughly elucidated, although a number of studies have repeatedly investigated them as candidate genes. [14][15][16][17][18][19][20] Moreover, we performed meta-analyses of the current data on the Japanese and the data from previous studies to verify consistency and to increase the statistical power of SNP trait associations.…”

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

“…'s study [21], [23] was higher than our current study, we considered that C79G polymorphism might associate with more severe hypertension. Our previous meta-analysis [27] also found the similar results, which suggested that C79G polymorphism was associated with ‘severe hypertension' defined on SBP≥160 mmHg and/or DBP≥95 mmHg, but no significant association could be found based on the current clinical diagnostic standard of hypertension on SBP≥140 mmHg and/or DBP≥90 mmHg [2]. Interestingly, further research was conducted to compare with Gu et al and Ge et al .…”