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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, r 2  = 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.

Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study