title: Association of an apolipoprotein E polymorphism with circulating cholesterols and hypertension: a meta-based Mendelian randomization analysis.
abstract: Prospective studies have reported that circulating cholesterol abnormalities are predictive of hypertension. As a test of the causal influence of circulating cholesterols on hypertension, we used a meta-based Mendelian randomization analysis to determine whether the apolipoprotein E (ApoE) gene polymorphism ɛ2/ɛ3/ɛ4 related to cholesterol changes is associated with hypertension. Data were available from 17 study populations, encompassing 2896 hypertensive patients and 2898 controls. A random effects model was applied irrespective of a between-study heterogeneity, and publication bias was examined using a funnel plot and Egger's test. An overall comparison of the ApoE gene alleles ɛ4 with ɛ3 yielded a significant 81% increased risk for hypertension (95% confidence interval (95% CI): 1.41-2.32; P<0.0005). Restricting the analysis to populations of Asian descent resulted in a 1.87-times higher likelihood of developing hypertension (95% CI: 1.41-2.32; P<0.0005). Compared with ɛ3 carriers, ɛ4 allele carriers had significantly higher levels of total cholesterol (standardized mean difference (SMD)=0.39; 95% CI: 0.2-0.57; P<0.0005) and low-density lipoprotein cholesterol (SMD=0.43; 95% CI: 0.23-0.64; P<0.0005). The predicted odds ratio (OR) for a 1 mmol l(-1) increase in total cholesterol was 4.58 (95% CI: 1.83-67.21) when all qualified studies were included and 4.98 (95% CI: 1.94-76.36) for Asian-descent populations. Similarly, the predicted OR for a 1-mmol l(-1) increase of low-density lipoprotein cholesterol was 3.97 (95% CI: 1.71-43.48) in all populations and 4.29 (95% CI: 1.81-43.38) in Asian-descent populations. Taken together, our findings suggest a casual influence of high circulating total cholesterol and low-density lipoprotein cholesterol levels on the development of hypertension.
authors: State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Wenquan
authors: W
authors: Niu
authors: Xuezhi
authors: X
authors: Zhang
authors: Yue
authors: Y
authors: Qi
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002784:Cholesterol / Q000097:blood* / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood / Q000235:genetics; D057182:Mendelian Randomization Analysis; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D002784:Cholesterol