Alicja E Grzegorzewska1, Dariusz Bednarski2, Monika Świderska1, Adrianna Mostowska3, Paweł P Jagodziński3. 1. Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland. 2. Student Nephrology Research Group, Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland. 3. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznań, Poland.
Abstract
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(A<G)_rs1801725(G>T) 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 (Pcorrected = 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.
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 HDpatients. 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. CASRrs7652589(A<G)_rs1801725(G>T) 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 (Pcorrected = 0.009). CASRrs7652589_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). CASRrs7652589_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). CASRrs1801725 did not show epistatic interactions with vitamin D signaling pathway genes concerning tested associations. CONCLUSION: The variant allele of CASRrs1801725 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 HDpatients.
Authors: Marciana L Laster; Bryce Rowan; Hua-Chang Chen; Tae-Hwi Schwantes-An; Xin Sheng; Peter A Friedman; T Alp Ikizler; Janet S Sinshiemer; Joachim H Ix; Katalin Susztak; Ian H de Boer; Bryan Kestenbaum; Adriana Hung; Sharon M Moe; Farzana Perwad; Cassianne Robinson-Cohen Journal: J Clin Endocrinol Metab Date: 2022-08-18 Impact factor: 6.134
Authors: Buthaina E Alathari; Arif Sabta Aji; Utami Ariyasra; Sri R Sari; Nabila Tasrif; Finny F Yani; Ikhwan R Sudji; Julie A Lovegrove; Nur I Lipoeto; Karani S Vimaleswaran Journal: Nutrients Date: 2021-01-23 Impact factor: 5.717