ATP2B1 and blood pressure: from associations to pathophysiology

Purpose of review Recent genome-wide association studies (GWAS) have revealed that the ATP2B1 gene is associated with hypertension not only in people of European origin, but also in Japanese, Chinese, and Koreans. However, ATP2B1 has never been considered to be a candidate gene for essential hypertension. Thus, this review summarizes the findings obtained in GWAS regarding the role of the ATP2B1 gene in essential hypertension, as well as recent suggestions about the mechanisms responsible for the effects of the ATP2B1 gene on calcium homeostasis. We also review the findings of studies involving spontaneously hypertensive rats and tissue-specific ATP2B1 knockout mice examining the effects of ATP2B1 on hypertension. Recent findings The ATP2B1 gene has been revealed to be a hypertension-susceptibility gene in large-scale GWAS studies. Meta-analysis of the ATP2B1 gene polymorphisms associated with hypertension confirmed that ATP2B1 is significantly associated with hypertension in East Asians. Moreover, vascular smooth muscle cell ATP2B1 knockout mice exhibited high blood pressure in radio telemetry-based experiments. Summary The ATP2B1 gene has been demonstrated to have a strong influence on blood pressure. Detailed analysis of tissue-specific knockout mice is expected to further confirm the role of ATP2B1 in the near future.