Association of germline variants and cardiovascular complications in primary aldosteronism

Abstract

It is estimated that as many as 40 million people in Japan have hypertension. Despite the fact that high blood pressure left untreated increases the risk of stroke and heart disease, approximately two out of three hypertensive patients do not have their blood pressure controlled at optimal levels. A significant contributing factor to this issue is the presence of "secondary hypertension", where high blood pressure is caused by an underlying medical conditions or other identifiable factors.

Primary aldosteronism (PA), the prevailing form of secondary hypertension, holds particular importance in hypertension management due to its heightened propensity to induce cardiovascular complications compared to primary hypertension without PA. Unfortunately, PA often goes undiagnosed, leading to a substantial number of potentially undetected cases. Moreover, some PA patients exhibit poor responsiveness to oral medication, necessitating surgical intervention, yet determining the appropriate indications and timing for surgery poses a challenge.

Until recently, genetic factors of PA have been largely unknown, but recently, genome-wide association study (GWAS), a method in the field of statistical genetics, has revealed genotypes associated with PA. However, these findings lack comprehensive sub-group analyses based on severity and disease types.Also, they necessitate validation among Japanese patients.

Our study aims to pinpoint genetic factors linked to PA, dissecting variances in severity and disease types among Japanese PA patients. By comparing the genotypes of PA patients with those unaffected by PA, we'll conduct thorough statistical analyses to identify the genotypes correlated with PA. The outcomes of this research are anticipated not only to deepen our understanding of PA's pathogenesis but also to enable precision medicine, leveraging genomic information and other test findings tailored to each patient.

In this study, we will utilize samples stored in the National Center Biobank Network (NCBN), which is supported by the Japan Health Research Promotion Bureau (JH). This comprehensive approach aims to yield more robust and reliable results.

Perspectives

Our goal is to better understand the pathogenesis of PA, and furthermore, to contribute to the formulation of a more refined clinical guideline for PA that utilizes genomic information.

Comments from principal researcher

Department of Cardiovascular Medicine, National Center for Global Health and Medicine, Daiki Tomidokoro

Some hypertensive patients are affected by primary aldosteronism (PA), an adrenal condition with a distinct pathogenesis compared to typical hypertension. Although the genetic causes of PA remain predominantly unidentified, their elucidation could not only advance our comprehension of hypertension and PA but also potentially refine individualized medical care. This study aims to contribute to this area, hoping to unveil these genetic causes to better understand the mechanisms behind hypertension and PA, ultimately striving to optimize medical care for each patient.

Shared Researchers

Senior Researcher, Medical Genome Center, National Cerebral and Cardiovascular Center, Sonoda Keiko