Division of Nephrology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Cleveland Clinic Lerner College of Medicine and Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
J Clin Endocrinol Metab. 2020 Jun 1;105(6). doi: 10.1210/clinem/dgz257.
To date, the effect of positive family history as a risk factor of primary aldosteronism (PA) is largely unknown. Studies have failed to distinguish the heritability of PA as well as the associations between positive family history of PA and clinical outcomes.
We quantified the prevalence, the extent of familial aggregation, the heritability of PA among family members of patients with PA, and the association between positive PA family history and major cardiovascular events (MACE).
Using the Taiwan National Health Insurance Database, 30 245 077 National Health Insurance beneficiaries (both alive and those deceased between January 1, 1999, and December 31, 2015) were identified.
We identified 7902 PA patients. Forty-four had PA (0.3%) among 10 234 individuals with affected parents, 2298 with affected offspring, 1924 with affected siblings, and 22 with affected twins. A positive family history was associated with the adjusted relative risk (RR) (95% confidence interval [CI]) of 11.60 (7.63-17.63) for PA in people with an affected first-degree relative. In subgroup analysis, the risk for PA across all relationships (parent, siblings, offspring, and spouse) showed highly significant differences to PA without family history. The accountability for phenotypic variance of PA was 51.0% for genetic factors, 24.9% for shared environmental factors, and 24.1% for nonshared environmental factors. PA patients with an affected first-degree relative were associated with an increased risk for composite major cardiovascular events (RR 1.31; 95% CI 1.24-1.40, P < .001) compared with PA patients without family history.
Familial clustering of PA exists among a population-based study, supporting a genetic susceptibility leading to PA. There is increased coaggregation of MACE in first-degree relatives of PA patients. Our findings suggest a strong genetic component in the susceptibility of PA, involving different kinships.
目前，阳性家族史作为原发性醛固酮增多症（PA）的危险因素的影响尚不清楚。研究未能区分 PA 的遗传性以及 PA 的阳性家族史与临床结局之间的关系。
我们量化了 PA 患者的家庭成员中 PA 的患病率、家族聚集程度、遗传性以及阳性 PA 家族史与主要心血管事件（MACE）之间的关系。
利用台湾全民健康保险数据库，我们确定了 30245077 名全民健康保险受保人（包括 1999 年 1 月 1 日至 2015 年 12 月 31 日期间的存活者和死亡者）。
我们共确定了 7902 例 PA 患者。在 10234 名有患病父母、2298 名有患病子女、1924 名有患病兄弟姐妹和 22 名有患病双胞胎的个体中，有 44 人患有 PA（0.3%）。阳性家族史与一级亲属中有患病者的 PA 调整后的相对风险（RR）（95%置信区间[CI]）为 11.60（7.63-17.63）相关。在亚组分析中，所有关系（父母、兄弟姐妹、子女和配偶）中 PA 的风险与无家族史的 PA 差异具有高度统计学意义。PA 的表型方差的可归因于遗传因素的比例为 51.0%，可归因于共享环境因素的比例为 24.9%，可归因于非共享环境因素的比例为 24.1%。与无家族史的 PA 患者相比，一级亲属中有患病者的 PA 患者发生复合主要心血管事件的风险增加（RR 1.31；95%CI 1.24-1.40，P<.001）。
在一项基于人群的研究中，PA 存在家族聚集现象，支持遗传易感性导致 PA。PA 患者的一级亲属中 MACE 的共聚集增加。我们的研究结果表明，PA 的易感性存在很强的遗传成分，涉及不同的亲属关系。
