CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy.
CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy.
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CYP2D6、GST-M1 和 GST-T1 酶：甲状旁腺中的表达及其与早期肾脏替代治疗期间甲状旁腺激素浓度的关系。
DOI：
10.1046/j.1365-2125.2003.01832.x
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发表时间：
2003
影响因子：
3.4
通讯作者：
Fanti,Paolo
中科院分区：
文献类型：
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作者：
Yan,Feng-Xiang;Langub,MChris;Ihnen,MarkA;Hornung,Carlton;Juronen,Erkki;Rayens,MaryK;Cai,Wei-Min;Wedlund,PeterJ;Fanti,Paolo
目的研究终末期肾病患者甲状旁腺组织中细胞色素P450 2D6、谷胱甘肽转移酶M1和谷胱甘肽转移酶T1的表达特点，探讨这些酶的缺失与血清甲状旁腺激素水平之间的关系。方法取手术切除的人甲状旁腺组织，用免疫组织化学方法检测其细胞定位和细胞定位。对328例高加索人终末期肾病患者的血液进行了CYP2D6*3、*4、*5、*6、*7和GST-M1*0、GST-T1*0等位基因检测。临床化学数据和血清完整甲状旁腺激素(IPTH)浓度从患者的病历中获得。在277名患者中，同一实验室进行了所有的临床测试。结果在人甲状旁腺组织中存在CYP2D6、GST-M1和GST-T1。CYP2D6与甲状旁腺激素共定位于甲状旁腺主细胞。在终末期肾病人群中，18.2%[95%可信区间(CI)8.0，28.4]iPTH浓度五分之一(iPTH<； Pg m L−1)，2个五分位数为0(95%CI 0，7.5)，3个五分位数为1.8%(95%CI 0，9.3)，4个五分位数为9.1%(95%CI 1.5，16.7)，5个五分位数为16.7%(95%CI 6.8，2 6.5)(P= 0.001)。在12例CYP2D6缺陷型女性中，7例iPTH浓度在第1个五分位数，其余5个在第5个五分位。GST-M1和GST-T1酶缺陷者相对于血清iPTH浓度的频率分布更为均匀。据报道，在新诊断的终末期肾病患者中，缺乏CYP2D6和iPTH浓度之间存在关联。性别和伴随的GST-M1和/或GST-T1缺陷似乎进一步定义了这种关联。这些关联是否反映了代谢酶表达不足与肾功能衰竭继发表现的严重程度之间的因果关系仍有待确定。
AimsThe purpose of this research was to characterize CYP2D6, GST‐M1 and GST‐T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end‐stage renal disease.MethodsSurgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST‐M1 and GST‐T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end‐stage renal disease for genetic testing ofCYP2D6*3,*4,*5,*6,*7andGST‐M1*0andGST‐T1*0alleles. Clinical chemistry data and serum intact parathyroid hormone (iPTH) concentrations were obtained from patient medical records. In 277 of the patients, the same laboratory performed all clinical tests.ResultsCYP2D6, GST‐M1 and GST‐T1 were present in human parathyroid tissue. CYP2D6 was colocalized with parathyroid hormone in parathyroid chief cells. Within the end‐stage renal disease population, a nonfunctional CYP2D6 genotype was present in 18.2%[95% confidence interval (CI) 8.0, 28.4] of patients in the 1st iPTH concentration quintile (iPTH < 64 pg mL−1), in 0% (95% CI 0, 7.5) of those in the 2nd quintile, in 1.8% (95% CI 0, 9.3) of those in the 3rd quintile, in 9.1% (95% CI 1.5, 16.7) of those in the 4th quintile, and in 16.7% (95% CI 6.8, 26.5) of those in the 5th quintile (iPTH > 347 pg mL−1) (P= 0.001). Out of 12 CYP2D6‐deficient females, seven were in the 1st iPTH concentration quintile and the remaining five were in the 5th quintile. Patients deficient in the GST‐M1 and GST‐T1 enzymes displayed a far more uniform frequency distribution relative to serum iPTH concentrations.ConclusionsThe presence of CYP2D6, GST‐M1 and GST‐T1 in parathyroid cells was observed. An association is reported between a lack of CYP2D6 and iPTH concentrations in newly diagnosed end‐stage renal disease patients. Gender and concomitant deficiency in GST‐M1 and/or GST‐T1 appear to define this association further. It remains to be established whether these associations reflect a cause‐effect relationship between deficient expression of metabolizing enzymes and severity of secondary manifestation of renal failure.