ATP2B1 gene polymorphisms rs2681472 and rs17249754 are associated with susceptibility to hypertension and blood pressure levels: A systematic review and meta-analysis

OBJECTIVE: The present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension. METHODS: PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or β and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software. RESULTS: A total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10–1.28; rs2681472: OR = 1.15, 95%CI: 1.12–1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, β=1.01, 95%CI: 0.86–1.16, DBP, β=0.48, 95%CI: 0.30–0.66; rs2681472: SBP, β=0.92, 95%CI: 0.77–1.07, DBP, β=0.50, 95%CI: 0.42–0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13–1.20) than in East Asians (OR = 1.14, 95%CI: 1.10–1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10–1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10–1.17). CONCLUSIONS: Our study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.