{"title":"肾酶 rs2296545 变体通过改变与阻塞性睡眠呼吸暂停患者儿茶酚胺的结合亲和力来改善高血压的易感性。","authors":"Hangdong Shen, Jundong Yang, Wenjun Xue, Zhicheng Wei, Lilin Li, Jian Guan, Xinyi Li, Xiaolin Wu","doi":"10.1038/s41440-024-01850-0","DOIUrl":null,"url":null,"abstract":"Obstructive sleep apnea (OSA), a condition often linked with hypertension, has an undefined relationship with renalase, a protein known for regulating blood pressure. This study aimed to investigate the relationship between serum renalase levels as well as renalase functional single nucleotide polymorphism (SNP) rs2296545 variant and hypertension in a Han Chinese OSA population. 126 subjects underwent serum renalase detection, with linear regression being performed to evaluate the relationship between serum renalase levels and OSA-related traits. Additional 4275 subjects were obtained rs2296545 genotype information by SNP microarray. And binary logistic regression was used to assess the effect of rs2296545 on hypertension risk. Molecular dynamics simulation and molecular docking were utilized to access the protein structures and the interplay between protein and catecholamines of wild-type and rs2296545 mutant renalase. The results showed that serum renalase levels were significantly higher in the severe OSA group. Further analysis showed renalase levels were positively correlated with blood pressure in the non-OSA group and negatively correlated in the severe OSA group. For rs2296545 polymorphism analysis, the hypertension risk significantly increased for the recessive model CC/GG + CG (OR = 1.211, 95% CI: 1.025–1.431) and the additive model CC/CG (OR = 1.223, 95% CI: 1.025–1.458) in the severe OSA. The rs2296545 polymorphism affected protein structure, and led to increase binding free energy, weakening interactions between renalase and catecholamines. In conclusion, serum renalase levels had independent association with blood pressure. And rs2296545 polymorphism may influence on susceptibility to hypertension by altering protein ability to bind to catecholamines, which might contribute to the intervention of hypertension in the OSA population.","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41440-024-01850-0.pdf","citationCount":"0","resultStr":"{\"title\":\"Renalase rs2296545 variant improve hypertension susceptibility by modifying binding affinity to catecholamines in obstructive sleep apnea\",\"authors\":\"Hangdong Shen, Jundong Yang, Wenjun Xue, Zhicheng Wei, Lilin Li, Jian Guan, Xinyi Li, Xiaolin Wu\",\"doi\":\"10.1038/s41440-024-01850-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Obstructive sleep apnea (OSA), a condition often linked with hypertension, has an undefined relationship with renalase, a protein known for regulating blood pressure. This study aimed to investigate the relationship between serum renalase levels as well as renalase functional single nucleotide polymorphism (SNP) rs2296545 variant and hypertension in a Han Chinese OSA population. 126 subjects underwent serum renalase detection, with linear regression being performed to evaluate the relationship between serum renalase levels and OSA-related traits. Additional 4275 subjects were obtained rs2296545 genotype information by SNP microarray. And binary logistic regression was used to assess the effect of rs2296545 on hypertension risk. Molecular dynamics simulation and molecular docking were utilized to access the protein structures and the interplay between protein and catecholamines of wild-type and rs2296545 mutant renalase. The results showed that serum renalase levels were significantly higher in the severe OSA group. Further analysis showed renalase levels were positively correlated with blood pressure in the non-OSA group and negatively correlated in the severe OSA group. For rs2296545 polymorphism analysis, the hypertension risk significantly increased for the recessive model CC/GG + CG (OR = 1.211, 95% CI: 1.025–1.431) and the additive model CC/CG (OR = 1.223, 95% CI: 1.025–1.458) in the severe OSA. The rs2296545 polymorphism affected protein structure, and led to increase binding free energy, weakening interactions between renalase and catecholamines. In conclusion, serum renalase levels had independent association with blood pressure. And rs2296545 polymorphism may influence on susceptibility to hypertension by altering protein ability to bind to catecholamines, which might contribute to the intervention of hypertension in the OSA population.\",\"PeriodicalId\":13029,\"journal\":{\"name\":\"Hypertension Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41440-024-01850-0.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hypertension Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41440-024-01850-0\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hypertension Research","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41440-024-01850-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
摘要
阻塞性睡眠呼吸暂停(OSA)是一种常与高血压相关的疾病,它与肾酶的关系尚不明确,而肾酶是一种已知可调节血压的蛋白质。本研究旨在调查汉族OSA人群中血清肾酶水平以及肾酶功能单核苷酸多态性(SNP)rs2296545变异与高血压之间的关系。126 名受试者接受了血清肾酶检测,并通过线性回归评估了血清肾酶水平与 OSA 相关特征之间的关系。另有 4275 名受试者通过 SNP 芯片获得了 rs2296545 基因型信息。并采用二元逻辑回归评估 rs2296545 对高血压风险的影响。利用分子动力学模拟和分子对接技术研究了野生型和 rs2296545 突变型肾酶的蛋白质结构以及蛋白质与儿茶酚胺之间的相互作用。结果显示,严重 OSA 组的血清肾酶水平明显较高。进一步分析表明,非 OSA 组的肾酶水平与血压呈正相关,而严重 OSA 组的肾酶水平与血压呈负相关。在 rs2296545 多态性分析中,隐性模型 CC/GG + CG(OR = 1.211,95% CI:1.025-1.431)和加性模型 CC/CG(OR = 1.223,95% CI:1.025-1.458)在严重 OSA 中的高血压风险显著增加。rs2296545 多态性影响蛋白质结构,导致结合自由能增加,削弱肾酶与儿茶酚胺之间的相互作用。总之,血清肾酶水平与血压有独立关联。rs2296545多态性可能通过改变蛋白质与儿茶酚胺的结合能力来影响高血压的易感性,这可能有助于对OSA人群的高血压进行干预。
Renalase rs2296545 variant improve hypertension susceptibility by modifying binding affinity to catecholamines in obstructive sleep apnea
Obstructive sleep apnea (OSA), a condition often linked with hypertension, has an undefined relationship with renalase, a protein known for regulating blood pressure. This study aimed to investigate the relationship between serum renalase levels as well as renalase functional single nucleotide polymorphism (SNP) rs2296545 variant and hypertension in a Han Chinese OSA population. 126 subjects underwent serum renalase detection, with linear regression being performed to evaluate the relationship between serum renalase levels and OSA-related traits. Additional 4275 subjects were obtained rs2296545 genotype information by SNP microarray. And binary logistic regression was used to assess the effect of rs2296545 on hypertension risk. Molecular dynamics simulation and molecular docking were utilized to access the protein structures and the interplay between protein and catecholamines of wild-type and rs2296545 mutant renalase. The results showed that serum renalase levels were significantly higher in the severe OSA group. Further analysis showed renalase levels were positively correlated with blood pressure in the non-OSA group and negatively correlated in the severe OSA group. For rs2296545 polymorphism analysis, the hypertension risk significantly increased for the recessive model CC/GG + CG (OR = 1.211, 95% CI: 1.025–1.431) and the additive model CC/CG (OR = 1.223, 95% CI: 1.025–1.458) in the severe OSA. The rs2296545 polymorphism affected protein structure, and led to increase binding free energy, weakening interactions between renalase and catecholamines. In conclusion, serum renalase levels had independent association with blood pressure. And rs2296545 polymorphism may influence on susceptibility to hypertension by altering protein ability to bind to catecholamines, which might contribute to the intervention of hypertension in the OSA population.
期刊介绍:
Hypertension Research is the official publication of the Japanese Society of Hypertension. The journal publishes papers reporting original clinical and experimental research that contribute to the advancement of knowledge in the field of hypertension and related cardiovascular diseases. The journal publishes Review Articles, Articles, Correspondence and Comments.