Vitamin D receptor gene polymorphisms affect secondary hyperparathyroidism in hemodialyzed patients

Nagaba, Yasushi; Heishi, Masayuki; Tazawa, Hiromitsu; Tsukamoto, Yusuke; Kobayashi, Yuki

doi:10.1053/ajkd.1998.v32.pm9740163

Cited by 59 publications

(31 citation statements)

References 12 publications

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“…Also, a protective effect of the B allele has been reported in Japanese patients undergoing hemodialysis [49].…”

Section: Discussionmentioning

confidence: 94%

Profile of vitamin D receptor polymorphism Bsm I and FokI in end stage renal disease Egyptian patients on maintenance hemodialysis

Ha¹,

Mm²,

Ew³

2017

J Clini Nephrol

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Objective: In end stage renal disease, the synthesis of vitamin D is disturbed.Hyperparathyroidism is one of the key factors in the pathogenesis of many of the complications of dialysis mainly bone and cardiovascular complications.Aim:This study aimed at assessing vitamin D receptor gene polymorphisms BsmIand FokI in Egyptian patients with end stage renal disease on maintenance haemodialysis and the assosciation of these polymorphisms with cardiovascular complications and hyperparathyroidism among these patients. Methods:One hundred subjects, recruited from Medical Research Institute, from March to July 2014, divided into two main groups; the control group which included thirty apparently healthy subjects and the patients group which included seventy patients with end stage renal disease on maintenance haemodialysis with median 4 years. To all studied subjects, detailed history was taken, thorough physical examination, carotid intima media thickness, presence of plaques and ECG ischemic changes. Laboratory investigations included serum levels of: glucouse, urea, creatinine, uric acid, albumin, total cholesterol, low and high density lipoproteins, calcium, phosphorus, and CRP as well as plasma PTH level. For molecular studies, the detection of BsmI and FokI polymorphisms using polymerase chain reaction and restriction fragment length polymorphism (PCR / RFLP) technique.Results: 1.No statistically signifi cant difference could be detected in both BsmI and FokI gene polymorphisms between the hemodialysis patients and the controls, suggesting that the development of ESRD had no relation with either VDR BsmI or FokI gene polymorphisms.2.No statistically signifi cant difference were found in these polymorphisms between the hemodialysis patients with or without cardiovascular complications or between patients with PTH level less or more than 300 pg/ml. These results suggest that the development of cardiovascular complications and secondary hyperparathyroidism among Egyptian patients on maintenance haemodialysis cannot be attributed to these two gene polymorphisms. Conclusion:No association could be found between the variant alleles of BsmI and FokI gene polymorphisms and the development of ESRD, cardiovascular complications and secondary hyperparathyroidism among the studied samples of Egyptian patients on maintenance haemodialysis. Research

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“…Also, a protective effect of the B allele has been reported in Japanese patients undergoing hemodialysis [49].…”

Section: Discussionmentioning

confidence: 94%

Profile of vitamin D receptor polymorphism Bsm I and FokI in end stage renal disease Egyptian patients on maintenance hemodialysis

Ha¹,

Mm²,

Ew³

2017

J Clini Nephrol

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“…Serum phosphorus is another factor that may be directly involved in the progression of secondary hyperparathyroidism, independent of 1,25D and extracellular Ca [16, 17]. As for the mechanisms of action of these three major factors of secondary hyperparathyroidism, there are some reports on the influence of VDR gene polymorphism on parathyroid function and bone mineral in ESRD patients [9, 10, 11, 12, 13]. In this study, we investigated the relationship between the parathyroid responsiveness to changes in extracellular Ca and VDR gene polymorphism by manipulating the Ca concentration of the dialysate.…”

Section: Discussionmentioning

confidence: 99%

“…There have been some reports on the relationship between VDR gene polymorphism and bone mineral metabolism in osteoporosis patients [6, 7, 8]. Recently, there have also been reports on the relationship between VDR polymorphism and parathyroid hormone (PTH) as well as bone mineral density in ESRD patients subjected to renal replacement therapy [9, 10, 11, 12, 13]. We have previously indicated the possibility of the influence of Apa I fragment length polymorphism of the VDR gene on onset and progression of secondary hyperparathyroidism in Japanese ESRD patients [11].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Receptor Gene Polymorphism Detected by Digestion with Apa I Influences the Parathyroid Response to Extracellular Calcium in Japanese Chronic Dialysis Patients

Yokoyama

Sügimura²,

Kagami

et al. 2001

Nephron

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Background: To play its physiological role, 1,25(OH)₂D₃ must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca²⁺ in the dialysate. Methods: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca²⁺]_e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca²⁺ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. Results: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 ± 9.4%) than in group AA+Aa (19.7 ± 7.2%). There were no significant differences between the two groups in [Ca²⁺]_e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. Conclusions: The study results showed that the patients in group aa were more sensitive to changes in [Ca²⁺]_e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca²⁺]_e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.

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“…Secondary hyperparathyroidism is a progressive disease, causing a gradual increase in the calcium set point [95], conversion of parathyroid glands to nodular hyperplasia, eventually requiring parathyroidectomy. Calcitriol therapy not only suppresses PTH secretion but also has a specific antiproliferative effect on parathyroid cells [96, 97], reducing the requirement for parathyroidectomy [64]. …”

Section: An Iatrogenic Disease?mentioning

confidence: 99%

Causes and Consequences of Adynamic Bone Disease

Heaf¹

2001

Nephron

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Vitamin D receptor gene polymorphisms affect secondary hyperparathyroidism in hemodialyzed patients

Cited by 59 publications

References 12 publications

Profile of vitamin D receptor polymorphism Bsm I and FokI in end stage renal disease Egyptian patients on maintenance hemodialysis

Profile of vitamin D receptor polymorphism Bsm I and FokI in end stage renal disease Egyptian patients on maintenance hemodialysis

Vitamin D Receptor Gene Polymorphism Detected by Digestion with Apa I Influences the Parathyroid Response to Extracellular Calcium in Japanese Chronic Dialysis Patients

Causes and Consequences of Adynamic Bone Disease

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