Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study.
Background: There is scarce data on CASR associations with dyslipidemia. We investigated in hemodialysis (HD) patients whether CASR single nucleotide polymorphisms (SNPs) rs7652589 and rs1801725 have associations with dyslipidemia and show epistatic interactions with SNPs of the energy homeostasis-a...
| Published in: | BMC Nephrology Vol. 20; no. 1; pp. 1 - 10 |
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| Main Authors: | , , , , , |
| Format: | research Journal Article |
| Published: |
BioMed Central
11/27/2019
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=139892785&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 139892785 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14712369 1CI6 jtl: BMC Nephrology issn: 14712369 maglogo: N pubinfo: dt: 11/27/2019 vid: 20 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 139892785 139892785 NLM31775661 139892785 10.1186/s12882-019-1619-0 NLM31775661 139892785 ppf: 1 ppct: 9 formats: tig: atl: Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study. aug: au: Grzegorzewska, Alicja E. Frycz, Bartosz A. Świderska, Monika Niepolski, Leszek Mostowska, Adrianna Jagodziński, Paweł P. affil: Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland sug: subj: Kidney Failure, Chronic Epidemiology Hemodialysis Adverse Effects Kidney Failure, Chronic Therapy Hemodialysis Methods Kidney Failure, Chronic Metabolism Hyperlipidemia Calcium Binding Proteins Calcium Binding Proteins Metabolism Polymorphism, Genetic Aged Middle Age Cross Sectional Studies Intercellular Signaling Peptides and Proteins Male Gene Expression Profiling Methods Proteins Human Poland Female Validation Studies Comparative Studies Evaluation Research Multicenter Studies Aged: 65+ years Middle Aged: 45-64 years Male Female ab: Background: There is scarce data on CASR associations with dyslipidemia. We investigated in hemodialysis (HD) patients whether CASR single nucleotide polymorphisms (SNPs) rs7652589 and rs1801725 have associations with dyslipidemia and show epistatic interactions with SNPs of the energy homeostasis-associated gene (ENHO), retinoid X receptor α gene (RXRA), and liver X receptor α gene (LXRA).Methods: The study included 1208 HD subjects. For diagnosis of dyslipidemia, both K/DOQI criteria and atherogenic index ≥3.8 were used. CASR rs1801725 was genotyped by TaqMan SNP Genotyping Assay, other SNPs - by high-resolution melting curve analysis or polymerase chain reaction-restriction fragment length polymorphism, as appropriate. Relative transcript levels of CASR, ENHO, RXRA, and LXRA were measured in peripheral blood mononuclear cells. The occurrence of dyslipidemic phenotypes concerning tested polymorphisms was compared using models of inheritance. Haplotypes were estimated using the Haploview 4.2 software. Epistatic interactions between tested SNPs were analyzed using the logistic regression and epistasis option in the PLINK software.Results: Rs7652589 indicated a greater probability of atherogenic dyslipidemia in the dominant inheritance model (OR 1.4, 95%CI 1.0-2.0, P = 0.026), principally because of increased triglyceride (TG) levels. The rs1801725 variant allele was associated with a decreased probability of dyslipidemia characterized by non-HDL-cholesterol ≥130 mg/dL and TG ≥200 mg/dL (OR 0.6, 0.4-0.9, P = 0.012). There were no epistatic interactions between CASR and RXRA, LXRA, and ENHO regarding dyslipidemia. Both rs7652589 and rs1801725 SNPs were not in linkage disequilibrium (D' = 0.091, r2 = 0.003 for the entire HD group) and their haplotypes did not correlate with dyslipidemia. Relative CASR transcript was lower at a borderline significance level in patients harboring the rs1801725 variant allele compared with homozygotes of the major allele (0.20, 0.06-7.80 vs. 0.43, 0.04-5.06, P = 0.058). CASR transcript correlated positively with RXRA transcript (adjusted P = 0.001), LXRA transcript (adjusted P = 0.0009), ENHO transcript (borderline significance, adjusted P = 0.055), dry body weight (adjusted P = 0.035), and renal replacement therapy duration (adjusted P = 0.013).Conclusions: CASR polymorphisms (rs7652589, rs1801725) are associated with dyslipidemia in HD patients. CASR correlates with RXRA, LXRA, and ENHO at the transcript level. Further investigations may elucidate whether other CASR SNPs contribute to associations shown in this study. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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