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

Grzegorzewska, Alicja E.; Świderska, Monika; Mostowska, Adrianna; Warchoł, Wojciech; Jagodzińśki, Paweł P.

doi:10.1155/2016/2383216

Cited by 7 publications

(12 citation statements)

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“…A prospective study was conducted in 440 HD patients. They were selected from 532 patients without a history of renal transplantation who started the prospective study in January 2009 [ 35 , 36 ]. The initial data of the HD patients included in the prospective study were also incorporated into the cross-sectional study.…”

Section: Methodsmentioning

confidence: 99%

ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients

et al. 2018

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BackgroundThe energy homeostasis-associated gene (ENHO), retinoid X receptor alpha gene (RXRA), and liver X receptor alpha gene (LXRA) are involved in adipogenic/lipogenic regulation. We investigated whether single-nucleotide polymorphisms in these genes (ENHO rs2281997, rs72735260; RXRA rs749759, rs10776909, rs10881578; LXRA rs2279238, rs7120118, rs11039155) are associated with dyslipidaemia, related comorbidities and survival of haemodialysis (HD) patients also tested for T-helper (Th) cell interleukin genes (IL).MethodsThe study was carried out in 873 HD patients. Dyslipidaemia was diagnosed by the recommendations of the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines (2003); atherogenic dyslipidaemia was referred to if the TG/HDL cholesterol ratio was equal to or higher than 3.8. Genotyping of ENHO SNPs, LXRA SNPs, and IL12A rs568408 was carried out using HRM analysis. RXRA SNPs, IL12B rs3212227, and IL18 rs360719 were genotyped using PCR-RFLP analysis. The circulating adropin concentration was determined in 126 patients by enzyme-linked immunosorbent assay. Survival probability was analysed using the Kaplan-Meier method in 440 patients followed through 7.5 years.ResultsDyslipidaemia by K/DOQI was diagnosed in 459 patients (91% revealed hyper-LDL- cholesterolaemia), atherogenic dyslipidaemia was diagnosed in 454 patients, and 231 patients were free of dyslipidaemia by both criteria. The variant allele (T) of ENHO rs2281997 was associated with the hyper-LDL cholesterolaemic pattern of dyslipidaemia by K/DOQI. The frequency of atherogenic dyslipidaemia was lower in T-allele bearers than in CC-genotype patients. The rs2281997 T allele was associated with lower cardiovascular mortality in HD patients showing atherogenic dyslipidaemia. ENHO, RXRA, and LXRA showed epistatic interactions in dyslipidaemia. Circulating adropin was lower in atherogenic dyslipidaemia than in non-atherogenic conditions. RXRA rs10776909 was associated with myocardial infarction. Bearers of LXRA rs2279238, rs7120118 or rs11039155 minor alleles showed higher mortality. ENHO SNP positions fell within the same DNase 1 hypersensitivity site expressed in the Th1 cell line. Epistatic interactions occurred between rs2281997 and Th1 IL SNPs (rs360719, rs568408).ConclusionsAtherogenic dyslipidaemia occurs in HD patients in whom ENHO encodes less adropin. ENHO, RXRA, and LXRA SNPs, separately or jointly, are associated with dyslipidaemia, myocardial infarction, and survival in HD patients. Differences in the availability of transcription binding sites may contribute to these associations.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0708-4) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients

et al. 2018

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“…The genomic pathways are activated by the binding of 1, 25(OH) 2 D 3 to nuclear vitamin D receptor (VDR). The non-genomic pathways are activated via cell membrane receptors for vitamin D, and might be responsible for the rapid effects of the hormone [4]. However, most of the biological actions of vitamin D are believed to be exerted through the nuclear VDR mediated control of target genes [5].…”

Section: Introductionmentioning

confidence: 99%

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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“…In the 7-year prospective study, CASR rs7652589 was not associated with all-cause and cardiovascular mortality in HD subjects [26]. CASR polymorphic variants also had no impact on the occurrence of cardiovascular events and all-cause mortality in renal transplant recipients [36].…”

Section: Discussionmentioning

confidence: 99%

“…CASR rs7652589 SNP interacted with CCL2 rs1024611 SNP concerning nephrolithiasis-related ESRD which was complicated with near 39% of cases with chronic infective tubulointerstitial nephritis [6]. In the 7-year prospective study, CASR rs7652589 yielded a borderline significance concerning infection-related mortality in the dominant model of inheritance [26]. However, how CASR rs1801725 SNP influences outcomes of infectious diseases remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…CASR rs7652589 SNP and vitamin D signaling pathway gene SNPs were genotyped using previously described methods [6, 26] in all HD patients who were not tested for our earlier studies. Genetic testing included the SNPs in the following vitamin D signaling pathway genes: group-specific component protein, GC (rs7041, rs1155563, rs2298849), retinoid X receptor alpha, RXRA (rs10881578, rs10776909, rs749759), and vitamin D receptor, VDR (rs1544410, rs2228570).…”

Section: Methodsmentioning

confidence: 99%

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The Calcium-Sensing Receptor Gene Polymorphism rs1801725 and Calcium-Related Phenotypes in Hemodialysis Patients

Grzegorzewska

Bednarski

Świderska

et al. 2018

Kidney Blood Press Res

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Background/Aims: The calcium-sensing receptor gene (CASR) rs1801725 variant is responsible for a non-conservative amino-acid change (A986S) in the calcium-sensing receptor cytoplasmic tail. We hypothesized that rs1801725 polymorphism might be helpful in understanding Ca-related abnormalities in HD patients. Methods: In 1215 subjects (245 on cinacalcet), we determined the associations of rs1801725 with secondary hyperparathyroidism (sHPT)-related laboratory parameters, PTH-decreasing effect of cinacalcet hydrochloride, coronary artery disease (CAD), myocardial infarction (MI), nephrolithiasis-related ESRD, and mortality. CASR rs7652589(AT) haplotypes and rs1801725 epistatic interactions with vitamin D signaling pathway genes were examined for associations with selected phenotypes. Results: The rs1801725 variant allele showed an increasing independent effect on plasma PTH (P_corrected = 0.009). CASR rs7652589_rs1801725 AT haplotype was associated with 1.7-fold higher frequency of PTH levels over 437 pg/mL than the reference haplotype GG (P = 0.001). CASR rs7652589_rs1801725 AG haplotype was 1.5-fold more frequent in nephrolithiasis-related ESRD than the GG haplotype (P = 0.004). There were no significant associations between rs1801725, CAD, MI, and response to cinacalcet. Variant homozygosity of rs1801725 correlated independently with higher infection-related mortality compared with heterozygosity (HR 7.95, 95%CI 2.15 – 29.37, P = 0.003) and major homozygosity (HR 5.89, 95%CI 1.69 – 20.55, P = 0.040). CASR rs1801725 did not show epistatic interactions with vitamin D signaling pathway genes concerning tested associations. Conclusion: The variant allele of CASR rs1801725 solely and together with the variant allele of rs7652589 increases risk of more advanced sHPT. Homozygosity of the rs1801725 variant allele contributes to infection-related mortality in HD patients.

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

Cited by 7 publications

References 47 publications

ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients

ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients

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

The Calcium-Sensing Receptor Gene Polymorphism rs1801725 and Calcium-Related Phenotypes in Hemodialysis Patients

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