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

Abstract EN

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%, P c o r r = 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.