Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham AL.
Department of Epidemiology University of Alabama at Birmingham Birmingham AL.
J Am Heart Assoc. 2022 Jun 21;11(12):e025582. doi: 10.1161/JAHA.121.025582. Epub 2022 Jun 14.
Background Corin enzyme contributes to the processing of inactive natriuretic peptides to bioactive hormones. In Black individuals, Corin gene variants (rs111253292 [Q568P] and rs75770792 [T555I]) have been previously reported to have a modest association with blood pressure (BP) and hypertension. Methods and Results We evaluated the association of Corin genotype with BP traits, prevalent hypertension, and incident hypertension among self-identified 11 322 Black Americans in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study and the JHS (Jackson Heart Study) using multivariable-adjusted regression modeling. Multivariable-adjusted genotype-stratified differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and BNP (B-type natriuretic peptide) levels were assessed. Genotype-stratified and expression differences in healthy organ donor left atrial and left ventricular heart tissue (N=15) were also examined. The rs111253292 genotype was not associated with systolic BP (β±SE, 0.42±0.58; -1.24±0.82), diastolic BP (0.51±0.33; -0.41±0.46), mean arterial pressure (0.48±0.38; -0.68±0.51), and prevalent hypertension (odds ratio [OR], 0.93 [95% CI, 0.80-1.09]; OR, 0.79 [95% CI, 0.61-1.01]) in both REGARDS and JHS, respectively. The rs75770792 genotype was not associated with systolic BP (0.48±0.58; -1.26±0.81), diastolic BP (0.52±0.33; -0.33±0.45), mean arterial pressure (0.50±0.38; -0.63±0.50), and prevalent hypertension (OR, 1.02 [95% CI, 0.84-1.23]; OR, 0.87 [95% CI, 0.67-1.13]) in both cohorts, respectively. The Corin genotype was also not associated with incident hypertension (OR, 1.35 [95% CI, 0.94-1.93]; OR, 0.95 [95% CI, 0.64-1.39]) in the study cohorts. The NT-proBNP levels in REGARDS and BNP levels in JHS were similar between the Corin genotype groups. In heart tissue, the and expression was similar between the genotype groups. Conclusions gene variants observed more commonly in Black individuals are not associated with differences in NP expression, circulating NP levels, and BP or hypertension as previously reported in candidate gene studies. Understanding the genetic determinants of complex cardiovascular traits in underrepresented populations requires further evaluation.
背景 Corin 酶有助于将无活性的利钠肽加工成生物活性激素。在黑人中，Corin 基因变异（rs111253292[Q568P]和 rs75770792[T555I]）先前已被报道与血压（BP）和高血压有一定关联。
方法和结果 我们使用 REGARDS（地理和种族差异中风原因）研究和 JHS（杰克逊心脏研究）中自我认定的 11322 名美国黑人的多变量调整回归模型评估 Corin 基因型与 BP 特征、现患高血压和高血压发病的相关性。评估了 NT-proBNP（N 末端 pro-B 型利钠肽）和 BNP（B 型利钠肽）水平的基因型分层差异。还检查了健康器官供体左心房和左心室心脏组织（N=15）中 Corin 基因型表达的差异。
rs111253292 基因型与收缩压（β±SE，0.42±0.58；-1.24±0.82）、舒张压（0.51±0.33；-0.41±0.46）、平均动脉压（0.48±0.38；-0.68±0.51）和现患高血压（比值比[OR]，0.93[95%置信区间，0.80-1.09]；OR，0.79[95%置信区间，0.61-1.01]）均无相关性。rs75770792 基因型与收缩压（0.48±0.58；-1.26±0.81）、舒张压（0.52±0.33；-0.33±0.45）、平均动脉压（0.50±0.38；-0.63±0.50）和现患高血压（OR，1.02[95%置信区间，0.84-1.23]；OR，0.87[95%置信区间，0.67-1.13]）均无相关性。这两个队列的 Corin 基因型与高血压发病也无相关性（OR，1.35[95%置信区间，0.94-1.93]；OR，0.95[95%置信区间，0.64-1.39]）。REGARDS 中的 NT-proBNP 水平和 JHS 中的 BNP 水平在 Corin 基因型组之间相似。在心脏组织中，基因型组之间的 和 表达相似。
结论 先前在候选基因研究中观察到的黑人中更常见的 基因变异与 NP 表达、循环 NP 水平以及 BP 或高血压无差异相关。了解代表性不足人群中复杂心血管特征的遗传决定因素需要进一步评估。
