在CHARGE和Global BPgen血压相关全基因组关联研究结果中，细胞膜钙转运ATP酶1（ATP2B1）是唯一与血压水平和高血压均相关的基因。我们前期参与的东亚人群全基因组关联研究和最近进行的中国人群验证研究，也证实该基因与高血压相关。但发现的阳性位点均处于非编码区，仅起标记作用，无法解释其生物功能。因此我们推测，ATP2B1基因可能存在功能性突变位点，他们可降低钙-ATP酶活性，导致血管平滑肌细胞内钙浓度增高，血管张力增强而引起血压升高。为验证以上假设，我们拟在既往研究基础上进一步深入：1）利用已收集的高血压家系和前瞻性队列，系统筛查ATP2B1基因包括罕见变异在内的全部编码区突变，以发现与高血压及血管功能相关的功能位点；2）在5000例自然人群中，验证发现的阳性位点对于人群血压水平的影响；3）分析阳性位点对蛋白表达及活性的影响。从而阐释ATP2B1基因在高血压发生、发展中的作用。

In the results of genome wide association studies (GWAS) of Global Blood Pressure Genetics (Global BPgen) consortium and the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium, plasma membrane calcium transporting ATPase 1 (ATP2B1) was the unique gene that related to both blood pressure level and hypertension among the 14 highlight loci. In our previous study of Agen BP GWAS and replication in Chinese population, we also confirmed the association of ATP2B1 gene with hypertension. However, all the susceptive loci were at non-coding region, which acted as target only. Accordingly, we developed the following hypotheses: certain functional mutant may locate at ATP2B1 gene, which can reduce the activity of Ca2+-ATPase and increase the intracellular calcium concentration in vascular smooth muscular cell, and then induce hypertension. To identify functional SNPs conferring susceptibility to hypertension, we conducted a case-control study in hypertension family, prospective hypertension cohort and general population. The SNPs were selected according to the latest map of 1000 Genomes Project, including all the rare and common mutants in ATP2B1 gene region. Furthermore, the functional study would be performed to verify the pathogenesis of the susceptive loci.