Gender-Specific Association of ATP2B1 Variants with Susceptibility to Essential Hypertension in the Han Chinese Population.

Jin Xu,Su-Pei Hu,Mei Feng,Mi Zhou,Hai-Xia Qian,Lin-Dan Ji,Li-Ya Liu,Jia Su

doi:10.1155/2016/1910565

Jin Xu, Su-Pei Hu + Show 6 more

Open Access

https://doi.org/10.1155/2016/1910565

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Abstract

Previous genome-wide association studies (GWASs) found that several ATP2B1 variants are associated with essential hypertension (EHT). But the “genome-wide significant” ATP2B1 SNPs (rs2681472, rs2681492, rs17249754, and rs1105378) are in strong linkage disequilibrium (LD) and are located in the same LD block in Chinese populations. We asked whether there are other SNPs within the ATP2B1 gene associated with susceptibility to EHT in the Han Chinese population. Therefore, we performed a case-control study to investigate the association of seven tagSNPs within the ATP2B1 gene and EHT in the Han Chinese population, and we then analyzed the interaction among different SNPs and nongenetic risk factors for EHT. A total of 902 essential hypertensive cases and 902 normotensive controls were involved in the study. All 7 tagSNPs within the ATP2B1 gene were retrieved from HapMap, and genotyping was performed using the Tm-shift genotyping method. Chi-squared test, logistic regression, and propensity score analysis showed that rs17249754 was associated with EHT, particularly in females. The MDR analysis demonstrated that the interaction of rs2070759, rs17249754, TC, TG, and BMI increased the susceptibility to hypertension. Crossover analysis and stratified analysis indicated that BMI has a major effect on the development of hypertension, while ATP2B1 variants have a minor effect.

Highlights

Because of its high prevalence and substantial impact on several cardiovascular diseases, hypertension is considered a major contributor to the global health burden [1]
According to the P values and odds ratios (ORs), only G allele of rs17249754 is associated with essential hypertension (EHT) (P = 0.005, OR = 1.21 (1.06–1.39)) after correction for multiple testing
Inputting all covariates including age, gender, highdensity lipoprotein (HDL), total cholesterol (TC), TG, body mass index (BMI), smoking habit, and alcohol abuse, the propensity score analysis indicated that still only G allele of rs17249754 is associated with EHT (P = 0.007, OR = 1.21)

Summary

Introduction

Because of its high prevalence and substantial impact on several cardiovascular diseases, hypertension is considered a major contributor to the global health burden [1]. In 2009, based on a genome-wide association study (GWAS) conducted by the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium, genetic polymorphisms of ATP2B1 were found to be significantly related to systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension [7]. These SNPs were replicated in the European populations by the Global Blood Pressure Genetics (Global BPgen) Consortium [8]. We conducted a replication analysis to test the association of seven tagSNPs within the ATP2B1 gene and EHT in the Han Chinese population. We analyzed the interaction among different SNPs and nongenetic risk factors for EHT, which provided additional information on the role of ATP2B1 variants

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