Original Investigations: Dialysis Therapies
Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients

https://doi.org/10.1053/ajkd.2002.33399Get rights and content

Abstract

It is well known that genetic factors are involved in the progression of secondary hyperparathyroidism (HPT) in hemodialysis (HD) patients. The purpose of the present study is to determine the relationship between restriction fragment length polymorphisms (RFLPs) of the parathyroid hormone (PTH) gene and serum intact PTH levels in HD patients. Eighty-six HD patients not treated with vitamin D and 80 healthy controls were analyzed. PTH genotypes were determined by polymerase chain reaction and RFLPs of BstBI and DraII. The presence or absence of BstBI and DraII restriction sites of the PTH gene were indicated by B or b and D or d, respectively. There were no significant differences in frequencies of each genotype between HD patients and healthy controls. In HD patients, serum intact PTH levels in the Dd/dd genotype were significantly greater than those in the DD genotype (P < 0.02). However, there was no significant difference in serum intact PTH levels between Bb/bb and BB genotypes. Serum intact PTH levels in the non-BBDD haplotype were significantly greater than those in the BBDD haplotype (P < 0.01). Serum intact PTH levels correlated negatively with serum calcium (Ca) and magnesium (Mg) levels and positively with alkaline phosphatase levels in simple regression analysis. However, in forward stepwise multiple regression analysis, only serum Ca and Mg levels predicted serum intact PTH levels. We conclude that PTH genotypes may influence secondary HPT in HD patients. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Subjects

Eighty-six HD patients (50 men, 36 women; mean age, 64.0 ± 12.7 years) and 80 healthy age-matched controls (50 men, 30 women; mean age, 58.2 ± 15.3 years) in the same geographic areas were analyzed in this study. No medication that might affect serum intact PTH levels and BMD, such as vitamin D, vitamin D derivatives, corticosteroids, or estrogen, was administered to patients. Patients underwent HD for 4 hours three times weekly using Ca and magnesium (Mg) dialysate concentrations of 3 and 1.2

Clinical characteristics and genotype distribution of the PTH gene

We analyzed RFLPs of BstBI and DraII in the PTH gene in 86 HD patients. Clinical characteristics of the study population are listed in Table 1.

. Clinical Characteristics of HD Patients

Age (y)64.0 ± 12.7
Sex (men/women)50/36
z Score−0.29 ± 1.19
Body mass index20.4 ± 2.75
HD duration (mon)51.8 ± 34.5
Serum intact PTH (pg/mL)93.7 ± 76.0
ALP (IU/L)169.9 ± 87.6
Serum Ca (mg/dL)9.3 ± 1.0
Serum P (mg/dL)5.2 ± 1.0
Serum Mg (mg/dL)2.4 ± 0.5
Frequencies of PTH genotypes did not differ between HD patients (BB,

Discussion

Secondary HPT is an important complication in HD patients. Excess PTH secretion is associated with parathyroid gland hyperplasia. Three main factors, ie, decreases in serum ionized Ca and serum calcitriol levels and an increase in serum P levels, are involved in the excess stimulation of PTH secretion. In kidneys, PTH increases Ca reabsorption, stimulates P excretion, and activates renal synthesis of active vitamin D metabolites that stimulate the intestinal absorption of Ca and P. In bones,

References (20)

There are more references available in the full text version of this article.

Cited by (0)

Address reprint requests to Yasuhiko Tomino, MD, Professor, Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: [email protected]

0272-6386/02/3906-0018$35.00/0

View full text
Copyright © 2002 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.