Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, United States.
Department of Community and General Medicine, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Am J Physiol Heart Circ Physiol. 2023 Sep 1;325(3):H545-H552. doi: 10.1152/ajpheart.00321.2023. Epub 2023 Jul 7.
Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are produced in the heart and secreted into the circulation. As hormones, both peptides activate the guanylyl cyclase receptor A (GC-A), playing a role in blood pressure (BP) regulation. A significant role for ANP and BNP includes favorable actions in metabolic homeostasis. Sex-based high prevalence of risk factors for cardiovascular disease in males compared with females is well established, but sex-based differences on cardiometabolic protection have not been investigated in relation to ANP () and BNP () gene variants. We included 1,146 subjects in the general population from Olmsted County, Minnesota. Subjects were genotyped for the ANP gene variant rs5068 and BNP gene variant rs198389. Cardiometabolic parameters and medical records were reviewed. In the presence of the minor allele of rs5068, diastolic BP, creatinine, body mass index (BMI), waist measurement, insulin, and prevalence of obesity and metabolic syndrome were lower, whereas HDL was higher in males with only trends observed in females. We observed no associations of the minor allele with echocardiographic parameters in either males or females. Regarding rs198389 genotype, the minor allele was not associated with any BP, metabolic, renal, or echocardiographic parameters in either sex. In the general community, the minor allele of the ANP gene variant rs5068 is associated with a favorable metabolic phenotype in males. No associations were observed with the BNP gene variant rs198389. These studies support a protective role of the ANP pathway on metabolic function and underscore the importance of sex in relationship to natriuretic peptide responses. Males are characterized by lower ANP and BNP with greater prevalence of cardiometabolic disease. The ANP genetic variant rs5068 was associated with less metabolic dysfunction in males, whereas no metabolic profile was related to the BNP genetic variant rs198389 in the general population. ANP may play a more biological role in metabolic homeostasis compared with BNP in the general population with greater physiological metabolic actions in males compared with females.
心房利钠肽 (ANP) 和 B 型利钠肽 (BNP) 在心脏中产生并分泌到循环中。作为激素，两种肽都激活鸟苷酸环化酶受体 A (GC-A)，在血压 (BP) 调节中发挥作用。ANP 和 BNP 的一个重要作用包括在代谢稳态中发挥有利作用。与女性相比，男性心血管疾病危险因素的高发率具有明显的性别差异，但尚未研究与 ANP()和 BNP()基因变异相关的针对心脏代谢的保护作用的性别差异。我们纳入了明尼苏达州奥姆斯特德县的 1146 名普通人群作为研究对象。对这些受试者的 ANP 基因变异 rs5068 和 BNP 基因变异 rs198389 进行了基因分型。回顾了心脏代谢参数和病历。在 rs5068 的次要等位基因存在的情况下，男性的舒张压、肌酐、体重指数 (BMI)、腰围、胰岛素和肥胖及代谢综合征的患病率较低，而高密度脂蛋白胆固醇水平较高，女性中仅观察到趋势。我们没有观察到男性或女性中次要等位基因与超声心动图参数之间的任何关联。关于 rs198389 基因型，次要等位基因与男女两性的任何血压、代谢、肾脏或超声心动图参数均无关。在普通人群中，ANP 基因变异 rs5068 的次要等位基因与男性的有利代谢表型相关。在男女两性中均未观察到与 BNP 基因变异 rs198389 相关的任何关联。这些研究支持 ANP 途径对代谢功能的保护作用，并强调了性别与利钠肽反应之间的关系的重要性。男性的 ANP 和 BNP 水平较低，患心脏代谢疾病的患病率较高。ANP 基因变异 rs5068 与男性较少的代谢功能障碍相关，而一般人群中 BNP 基因变异 rs198389 与任何代谢特征均无关。与 BNP 相比，ANP 可能在普通人群中对代谢稳态具有更重要的生物学作用，因为其在男性中的生理代谢作用强于女性。
