The relationship between apolipoprotein E ɛ2/ɛ3/ɛ4 polymorphisms and hypertension: a meta-analysis of six studies comprising 1812 cases and 1762 controls

Abstract

We performed a meta-analysis in an effort to systematically explore the association between apolipoprotein E (ApoE) epsilon2/epsilon3/epsilon4 polymorphisms and hypertension. We searched for case-control studies in English-language publications performed with human subjects using MEDLINE and included appropriate studies that had been published as of 6 May 2009. Fixed-effects models were used to pool data when between-study heterogeneity was absent, and random-effects models were used otherwise. Data and study quality were assessed in duplicate. Publication bias was assessed by calculating the fail-safe number. From six heterogeneous studies that included a total of 1812 patients with hypertension and 1762 controls, we found that the ApoE epsilon4 allele was significantly associated with hypertension using a random-effects model (odds ratio (OR)=1.79; 95% confidence interval (CI): 1.04 to 1.19; P=0.04). With regard to ApoE genotypes, we observed that the association with hypertension was more prominent when ApoE4/4 was compared with E3/3, with a nearly twofold increased risk identified for the ApoE4/4 genotype using a random-effects model (OR=1.97; 95% CI: 1.11 to 3.52; P=0.02). Furthermore, after restricting our analysis to Asian populations, the contrasts between the risk of hypertension among individuals possessing ApoE epsilon4 vs. epsilon3 and ApoE4/4 vs. ApoE3/3 were positively reinforced, with ORs of 1.97 (95% CI, 0.93 to 4.15; P=0.08) and 2.27 (95% CI, 1.03 to 4.98; P=0.04), respectively. The fail-safe number supported these significant associations at a significance level of 0.05. Taken together, our meta-analysis expands the data available regarding genetic risk factors for hypertension by illustrating that the presence of the ApoE epsilon4 allele is associated with an increased risk of developing hypertension and that it appears to be recessive. Of note, this effect was more pronounced in Asians.

Association of an apolipoprotein E polymorphism with circulating cholesterols and hypertension: a meta-based Mendelian randomization analysis

“…Using a comprehensive meta-analysis, we determined that the ApoE gene polymorphism e2/e3/e4 is significantly associated with hypertension, which is in agreement with the results from two recent meta-analyses, 13,14 and is associated with large changes in circulating cholesterol levels. Under the rationale of the Mendelian randomization, we utilized this polymorphism as an instrumental variable, which is associated with circulating cholesterol levels, and we demonstrated the causal influence of high total cholesterol and low-density lipoprotein cholesterol levels on hypertension.…”

“…After our two recently published meta-analyses, which associated the ApoE gene polymorphism e2/e3/e4 with hypertension using the results from English-language literature 13 and from Chinese populations, 14 we focused on whether circulating cholesterol levels related to this polymorphism are causal factors in hypertension, drawing from published studies in English and Chinese. In this study, we only assessed e2/e3/e4 allelic association, so one study that provided combined genotype counts was removed.…”

“…The baseline characteristics of all the qualified studies was mirrored in the above two meta-analyses. 13,14 A total of 7 of the 19 studies provided information regarding the association between the polymorphism and cholesterol. The distribution of total cholesterol and high-and low-density lipoprotein cholesterol levels across the e2 (e2/2+e2/3), e3 (e3/3) and e4 (e3/4+e4/4) alleles is summarized in Table 1.…”

“…12 In particular, the ApoE gene polymorphism e2/e3/e4 is of significant interest, because two recent meta-analyses consistently suggested that e4 allele carriers were at increased risk for hypertension, and that this effect was more pronounced in Chinese populations. 13,14 Additionally, this polymorphism was reportedly linked to changes in cholesterol levels [15][16][17][18] and therefore should be associated with hypertension if a causality exists between cholesterol levels and hypertension.…”

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

“…The quality assessment score we used was adapted from Niu et al 12 and Zhang et al, 13 which were based on both traditional epidemiologic considerations and genetic issues raised by Thakkinstian et al 14,15 Total scores ranged from 0 (lowest) to 13 (highest). The criteria used for the quality assessment of the genetic association between the ADD1 Gly460Trp polymorphism and hypertension risk are summarized in the Appendix.…”