M. Behairy, Sahar Mahmoud Shawky, Somia Abdelhamid Bawady, H. Abdelsattar, Neveen Nabil Abdelsahheed, Ahmad Yehia Elhag
{"title":"钙传感受体基因多态性 CASR rs 1042636、CASR rs 1802757 与继发性甲状旁腺功能亢进症埃及血液透析患者西那卡西特反应的关系","authors":"M. Behairy, Sahar Mahmoud Shawky, Somia Abdelhamid Bawady, H. Abdelsattar, Neveen Nabil Abdelsahheed, Ahmad Yehia Elhag","doi":"10.34172/jpd.2024.11255","DOIUrl":null,"url":null,"abstract":"Introduction: Secondary hyperparathyroidism (SHPT) is a common complication associated with morbidity and mortality among hemodialysis (HD) patients. Objectives: The current study aims to evaluate the frequency of CASR gene polymorphism variants related to parathyroid hormone (PTH) regulation (CASR rs1042636 and CASR rs1802757) and to test the hypothesis that single nucleotide polymorphisms (SNPs) in the CASR gene alter the response to cinacalcet among Egyptian HD patients with SHPT. Patients and Methods: A case-control study that included 50 HD patients with intact parathyroid hormone (iPTH) ≥300 pg/mL treated with cinacalcet for a 6-month duration and 40 healthy volunteers as a control group. Eligible patients were recruited from Ain Shams university hospitals. Blood samples were collected from patients and controls to assess allele frequencies of CASR gene polymorphism variants using real-time polymerase chain reaction (PCR), corrected calcium (Ca), phosphorus (P), Ca×P product, iPTH level, and alkaline phosphatase before and after treatment. HD patients were categorized into two groups based on the reduction percentage; responders’ patients (iPTH ≥20%) and non-responders to cinacalcet treatment. Results: Of 50 HD patients, 48 (96%) carried the rs1042636 AA wild gene, while only two (4%) carried the rs1042636 AG mutant gene, 42 (87.5%) carried the rs1802757 CC wild genotype, and 6 (12.5%) carried the CT mutant genotype. The minor alleles T and G were (6.3% and 2%) respectively, with no statistically significant difference between the patient and control groups regarding the CASR genotypes or alleles distribution. There was no significant difference between responders and non-responder’s patient groups regarding CASR genotypes or allele frequencies. Moreover, no significant correlation between CASR genotypes or alleles to delta change of Ca, P, Ca×P product, or PTH was seen. However, CASR rs1802757 CT mutant genotype was associated with a significant reduction in alkaline phosphatase levels after treatment. Conclusion: There is no significant association between the gene polymorphism CASR rs1042636 or CASR rs1802757 and the reduction in PTH levels as a response to cinacalcet treatment among Egyptian HD patients with SHPT.","PeriodicalId":16657,"journal":{"name":"Journal of Parathyroid Disease","volume":"49 11","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Relationship of calcium-sensing receptor gene polymorphism CASR rs 1042636, CASR rs 1802757, and cinacalcet response among Egyptian hemodialysis patients with secondary hyperparathyroidism\",\"authors\":\"M. Behairy, Sahar Mahmoud Shawky, Somia Abdelhamid Bawady, H. Abdelsattar, Neveen Nabil Abdelsahheed, Ahmad Yehia Elhag\",\"doi\":\"10.34172/jpd.2024.11255\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Introduction: Secondary hyperparathyroidism (SHPT) is a common complication associated with morbidity and mortality among hemodialysis (HD) patients. Objectives: The current study aims to evaluate the frequency of CASR gene polymorphism variants related to parathyroid hormone (PTH) regulation (CASR rs1042636 and CASR rs1802757) and to test the hypothesis that single nucleotide polymorphisms (SNPs) in the CASR gene alter the response to cinacalcet among Egyptian HD patients with SHPT. Patients and Methods: A case-control study that included 50 HD patients with intact parathyroid hormone (iPTH) ≥300 pg/mL treated with cinacalcet for a 6-month duration and 40 healthy volunteers as a control group. Eligible patients were recruited from Ain Shams university hospitals. Blood samples were collected from patients and controls to assess allele frequencies of CASR gene polymorphism variants using real-time polymerase chain reaction (PCR), corrected calcium (Ca), phosphorus (P), Ca×P product, iPTH level, and alkaline phosphatase before and after treatment. HD patients were categorized into two groups based on the reduction percentage; responders’ patients (iPTH ≥20%) and non-responders to cinacalcet treatment. Results: Of 50 HD patients, 48 (96%) carried the rs1042636 AA wild gene, while only two (4%) carried the rs1042636 AG mutant gene, 42 (87.5%) carried the rs1802757 CC wild genotype, and 6 (12.5%) carried the CT mutant genotype. The minor alleles T and G were (6.3% and 2%) respectively, with no statistically significant difference between the patient and control groups regarding the CASR genotypes or alleles distribution. There was no significant difference between responders and non-responder’s patient groups regarding CASR genotypes or allele frequencies. Moreover, no significant correlation between CASR genotypes or alleles to delta change of Ca, P, Ca×P product, or PTH was seen. However, CASR rs1802757 CT mutant genotype was associated with a significant reduction in alkaline phosphatase levels after treatment. Conclusion: There is no significant association between the gene polymorphism CASR rs1042636 or CASR rs1802757 and the reduction in PTH levels as a response to cinacalcet treatment among Egyptian HD patients with SHPT.\",\"PeriodicalId\":16657,\"journal\":{\"name\":\"Journal of Parathyroid Disease\",\"volume\":\"49 11\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Parathyroid Disease\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.34172/jpd.2024.11255\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Parathyroid Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34172/jpd.2024.11255","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
简介:继发性甲状旁腺功能亢进症(SHPT)是血液透析(HD)患者中一种常见的并发症,与发病率和死亡率相关。研究目的本研究旨在评估与甲状旁腺激素(PTH)调节相关的 CASR 基因多态性变异(CASR rs1042636 和 CASR rs1802757)的频率,并检验 CASR 基因中的单核苷酸多态性(SNPs)是否会改变患有 SHPT 的埃及 HD 患者对西那卡塞的反应这一假设。患者和方法:病例对照研究:50 名甲状旁腺激素(iPTH)≥ 300 pg/mL 的 HD 患者接受为期 6 个月的西那卡塞治疗,40 名健康志愿者作为对照组。符合条件的患者来自艾因夏姆斯大学医院。采集患者和对照组的血样,使用实时聚合酶链式反应(PCR)评估 CASR 基因多态性变异的等位基因频率、治疗前后的校正钙(Ca)、磷(P)、Ca×P 乘积、iPTH 水平和碱性磷酸酶。根据降低的百分比将 HD 患者分为两组:对西那卡西酮治疗有反应的患者(iPTH ≥20%)和无反应的患者。结果在 50 名 HD 患者中,48 人(96%)携带 rs1042636 AA 野生基因,只有 2 人(4%)携带 rs1042636 AG 突变基因,42 人(87.5%)携带 rs1802757 CC 野生基因型,6 人(12.5%)携带 CT 突变基因型。小等位基因 T 和 G 的比例分别为 6.3% 和 2%,在 CASR 基因型或等位基因分布方面,患者组和对照组之间没有显著的统计学差异。在 CASR 基因型或等位基因频率方面,有反应和无反应患者组之间没有明显差异。此外,CASR基因型或等位基因与Ca、P、Ca×P乘积或PTH的δ变化之间也没有明显的相关性。不过,CASR rs1802757 CT 突变基因型与治疗后碱性磷酸酶水平的明显降低有关。结论在患有 SHPT 的埃及 HD 患者中,CASR rs1042636 或 CASR rs1802757 基因多态性与 PTH 水平的降低(对西那卡西特治疗的反应)之间没有明显关联。
Relationship of calcium-sensing receptor gene polymorphism CASR rs 1042636, CASR rs 1802757, and cinacalcet response among Egyptian hemodialysis patients with secondary hyperparathyroidism
Introduction: Secondary hyperparathyroidism (SHPT) is a common complication associated with morbidity and mortality among hemodialysis (HD) patients. Objectives: The current study aims to evaluate the frequency of CASR gene polymorphism variants related to parathyroid hormone (PTH) regulation (CASR rs1042636 and CASR rs1802757) and to test the hypothesis that single nucleotide polymorphisms (SNPs) in the CASR gene alter the response to cinacalcet among Egyptian HD patients with SHPT. Patients and Methods: A case-control study that included 50 HD patients with intact parathyroid hormone (iPTH) ≥300 pg/mL treated with cinacalcet for a 6-month duration and 40 healthy volunteers as a control group. Eligible patients were recruited from Ain Shams university hospitals. Blood samples were collected from patients and controls to assess allele frequencies of CASR gene polymorphism variants using real-time polymerase chain reaction (PCR), corrected calcium (Ca), phosphorus (P), Ca×P product, iPTH level, and alkaline phosphatase before and after treatment. HD patients were categorized into two groups based on the reduction percentage; responders’ patients (iPTH ≥20%) and non-responders to cinacalcet treatment. Results: Of 50 HD patients, 48 (96%) carried the rs1042636 AA wild gene, while only two (4%) carried the rs1042636 AG mutant gene, 42 (87.5%) carried the rs1802757 CC wild genotype, and 6 (12.5%) carried the CT mutant genotype. The minor alleles T and G were (6.3% and 2%) respectively, with no statistically significant difference between the patient and control groups regarding the CASR genotypes or alleles distribution. There was no significant difference between responders and non-responder’s patient groups regarding CASR genotypes or allele frequencies. Moreover, no significant correlation between CASR genotypes or alleles to delta change of Ca, P, Ca×P product, or PTH was seen. However, CASR rs1802757 CT mutant genotype was associated with a significant reduction in alkaline phosphatase levels after treatment. Conclusion: There is no significant association between the gene polymorphism CASR rs1042636 or CASR rs1802757 and the reduction in PTH levels as a response to cinacalcet treatment among Egyptian HD patients with SHPT.