Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study

We evaluated in the 7-year prospective study whether variants in vitamin D pathway genes and calcium-sensing receptor gene (CASR) are determinants of mortality in hemodialysis (HD) patients (n=532). HRM analysis was used for GC rs2298849, GC rs1155563, RXRA rs10776909, RXRA rs10881578, and CASR rs76...

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Main Authors: Alicja E. Grzegorzewska, Monika K. Świderska, Adrianna Mostowska, Wojciech Warchoł, Paweł P. Jagodziński
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2016/2383216
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author Alicja E. Grzegorzewska
Monika K. Świderska
Adrianna Mostowska
Wojciech Warchoł
Paweł P. Jagodziński
author_facet Alicja E. Grzegorzewska
Monika K. Świderska
Adrianna Mostowska
Wojciech Warchoł
Paweł P. Jagodziński
author_sort Alicja E. Grzegorzewska
collection DOAJ
description We evaluated in the 7-year prospective study whether variants in vitamin D pathway genes and calcium-sensing receptor gene (CASR) are determinants of mortality in hemodialysis (HD) patients (n=532). HRM analysis was used for GC rs2298849, GC rs1155563, RXRA rs10776909, RXRA rs10881578, and CASR rs7652589 genotyping. GC rs7041, RXRA rs749759, VDR rs2228570, and VDR rs1544410 were genotyped using PCR-RFLP analysis. The minor allele in GC rs2298849 was associated with all-cause mortality in univariate analysis (HR 1.330, 95% CI 1.046–1.692, P=0.020). Bearers of the minor allele in GC rs2298849 demonstrated higher infection/neoplasm mortality than major allele homozygotes also in multivariate analysis (HR 2.116, 95% CI 1.096–4.087, P=0.026). Cardiovascular mortality was associated with major homozygosity (CC) in VDR rs2228570 (HR 1.896, 95% CI 1.163–3.091, P=0.010). CC genotype patients were more often dyslipidemic than TT genotype subjects (46.1% versus 31.9%, P=0.047). Dyslipidemics showed higher frequency of rs1544410_rs2228570 haplotype AC than nondyslipidemics (26 versus 18%, Pcorr=0.005), whereas TT genotype patients were at lower risk of dyslipidemia compared with CC/CT genotype patients (HR 0.59, 95% CI 0.37–0.96, P=0.04). In conclusion, GC rs2298849 and VDR rs2228570 SNPs are associated with survival on HD. VDR-related cardiovascular mortality may occur due to connections of rs2228570 with dyslipidemia.
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spelling doaj-art-d73911f104494fa88de8e33e0915078f2025-02-03T01:31:56ZengWileyInternational Journal of Endocrinology1687-83371687-83452016-01-01201610.1155/2016/23832162383216Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational StudyAlicja E. Grzegorzewska0Monika K. Świderska1Adrianna Mostowska2Wojciech Warchoł3Paweł P. Jagodziński4Chair and Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, PolandStudent Nephrology Research Group, Chair and Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, PolandChair and Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Święcickiego 6, 60-781 Poznań, PolandChair and Department of Biophysics, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Święcickiego 6, 60-781 Poznań, PolandWe evaluated in the 7-year prospective study whether variants in vitamin D pathway genes and calcium-sensing receptor gene (CASR) are determinants of mortality in hemodialysis (HD) patients (n=532). HRM analysis was used for GC rs2298849, GC rs1155563, RXRA rs10776909, RXRA rs10881578, and CASR rs7652589 genotyping. GC rs7041, RXRA rs749759, VDR rs2228570, and VDR rs1544410 were genotyped using PCR-RFLP analysis. The minor allele in GC rs2298849 was associated with all-cause mortality in univariate analysis (HR 1.330, 95% CI 1.046–1.692, P=0.020). Bearers of the minor allele in GC rs2298849 demonstrated higher infection/neoplasm mortality than major allele homozygotes also in multivariate analysis (HR 2.116, 95% CI 1.096–4.087, P=0.026). Cardiovascular mortality was associated with major homozygosity (CC) in VDR rs2228570 (HR 1.896, 95% CI 1.163–3.091, P=0.010). CC genotype patients were more often dyslipidemic than TT genotype subjects (46.1% versus 31.9%, P=0.047). Dyslipidemics showed higher frequency of rs1544410_rs2228570 haplotype AC than nondyslipidemics (26 versus 18%, Pcorr=0.005), whereas TT genotype patients were at lower risk of dyslipidemia compared with CC/CT genotype patients (HR 0.59, 95% CI 0.37–0.96, P=0.04). In conclusion, GC rs2298849 and VDR rs2228570 SNPs are associated with survival on HD. VDR-related cardiovascular mortality may occur due to connections of rs2228570 with dyslipidemia.http://dx.doi.org/10.1155/2016/2383216
spellingShingle Alicja E. Grzegorzewska
Monika K. Świderska
Adrianna Mostowska
Wojciech Warchoł
Paweł P. Jagodziński
Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study
International Journal of Endocrinology
title Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study
title_full Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study
title_fullStr Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study
title_full_unstemmed Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study
title_short Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study
title_sort polymorphisms of vitamin d signaling pathway genes and calcium sensing receptor gene in respect to survival of hemodialysis patients a prospective observational study
url http://dx.doi.org/10.1155/2016/2383216
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