Clinical aspects of vitamin D-binding protein gene polymorphisms in hemodialysis patients

Abstract

MI,11 while mineral bone disorders, including secondary hyperparathyroidism (HPT), were reported as more severe in uremic women than in men. [12][13][14] Sex-specific effects of vitamin D were also demonstrated in mice. 15Decreased plasma 25(OH)D levels may be caused by insufficient levels of circulating vitamin D-binding protein (DBP), which has a spectrum of biological activities (actin scavenging, fatty acid transport, macrophage activation, and chemotaxis) and transports vitamin D to its receptors in target tissues.16 Lower baseline plasmais a widely accepted biomarker of the vitamin D status, also in end-stage renal disease (ESRD). 1 Patients with ESRD, including those on hemodialysis (HD), usually have low plasma vitamin D levels. 2,3Vitamin D deficiency is epidemiologically linked to life-threatening diseases such as myocardial infarction (MI), 4-6 cerebral stroke, 5 and bone fractures, 7 the prevalence of which is related to sex. 4,[8][9][10] In dialysis patients, the above conditions are more frequent than in the general population. Male sex was shown to be associated with a higher frequency of OBJECTIVES We evaluated the frequency distribution of GC polymorphic variants in hemodialysis (HD) patients and healthy subjects as well as the differences in the prevalence of coronary artery disease (CAD) and myocardial infarction (MI) and selected clinical and laboratory indices of secondary hyperparathyroidism in HD patients (women and men) with different GC polymorphic variants.PATIENTS AND METHODS HD patients (n = 1056; 625 men) and healthy controls (n = 313; 150 men) were enrolled into the study. The tested GC polymorphisms included rs2298849, rs7041, and rs1155563. We analyzed clinical data (prevalence of CAD and MI; treatment with parathyroidectomy or cinacalcet) and laboratory results (serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxy vitamin D [25(OH)D) in relation to the gene polymorphisms.RESULTS There were no differences between the study groups themselves and between the study groups and controls in terms of the frequency distribution of GC polymorphisms (P trend <0.05). Lower plasma 25(OH)D levels were shown in subjects with the rs7041 TT genotype compared with those with the GG genotype (12.7, 5.7-20.9 ng/ml vs. 15.9, 8.0-50.0 ng/ml, P = 0.02). Women with the rs7041 TT genotype compared with those with the GG genotype showed higher serum phosphorus levels (5.58, 3.40-8.97 mg/dl vs. 5.03, 1.75-9.33 mg/dl, P = 0.007).CONCLUSIONS HD patients do not differ in the distribution of GC polymorphisms rs2298849, rs7041, and rs1155563 from healthy subjects. In HD patients, the GC polymorphism is associated with plasma 25(OH)D levels. Sex-related factors may be important in the expression of associations between GC polymorphic variants and mineral disorders.

Self-Reported Physical Activity, Quality of Life, and Psychological Status in Relation to Plasma 25-Hydroxyvitamin D Concentration in Patients Treated with Hemodialysis

“…We confirmed in this respect previous studies [38,40]. In patients bearing the minor allele of GC rs7041, a substitution of aspartic acid to glutamic acid at amino acid position 432 (Asp432Glu) of vitamin D binding protein attributed to the functional properties of the GC rs7041 variant seems to be an important contributor to decreased plasma 25(OH)D levels, possible by inducing a lower affinity of 25(OH)D to vitamin D binding protein.…”

“…Recognition of variables significantly influencing plasma 25(OH)D concentration may be of relevance for the understanding of 25(OH)D associations with psychological characteristics. Among such variables there are genetic polymorphisms in GC (rs2282679, rs7041, rs1155563) [38,40], gender [16,38], sunlight exposure [14,15], dialysis modality [16], and BMI [15,41].…”

“…The genotyping of GC rs1155563 nucleotide variants was conducted by high-resolution melting curve analysis (HRM) on the Bio-Rad CFX96 Real Time PCR system (Bio-Rad, Hercules, California, United States). Primer sequences and conditions for PCR-RFLP and HRM analyses are presented in the earlier study [38].…”

T helper cell‑related cytokine gene polymorphisms and vitamin D pathway gene polymorphisms as predictors of survival probability in patients on renal replacement therapy

“…50 The VDR rs1 544410 AA genotype was shown to play a negative role (but not as an independent factor) in determining response to hepatitis B vaccination in patients from the study group. 51 Moreover, 2 of the tested SNPs of GC (rs7041, rs1155563) were identified as associated with 25(OH)D concentrations in a European population in a genome-wide association study.…”

Does combination of paricalcitol with cinacalcet in secondary hyperparathyroidism in hemodialysis treatment make sense?

“…25 the GC polymorphism was associated with plasma 25(OH)D levels in this population. 43 On the other hand, vitamin D pathway genes were not associated with survival probability of patients on renal replacement therapy.…”