title: Study of the association between ITPKC genetic polymorphisms and calcium nephrolithiasis.
abstract: Nephrolithiasis is a multifactorial disease caused by environmental, hormonal, and genetic factors. Genetic polymorphisms of ORAI1, which codes for the main subunit of the store-operated calcium (SOC) channel, were reported to be associated with the risk and recurrence of calcium nephrolithiasis. Inositol 1,4,5-trisphosphate (IP3) 3-kinase C (ITPKC) is a negative regulator of the SOC channel-mediated signaling pathway. We investigated the association between calcium containing nephrolithiasis and genetic variants of ITPKC gene in Taiwanese patients. 365 patients were recruited in this study. Eight tagging single nucleotide polymorphisms of ITPKC were selected for genotyping. ITPKC genotypes were determined by TaqMan assay. ITPKC plasmids were transfected into cells to evaluate the intracellular calcium mobilization. Our results indicated that rs2607420 CC genotype in the intron region of the ITPKC gene is associated with a lower eGFR by both Modification of Diet in Renal Diseases (P = 0.0405) and Cockcroft-Gault (P = 0.0215) equations in patients with calcium nephrolithiasis. Our results identify a novel polymorphism for renal function and highlight the importance of ITPKC as a key molecule to regulate calcium signaling.
authors.affiliation: Department of Nephrology, Chi-Mei Medical Center, Tainan 710, Taiwan ; Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan.
authors.forename: Wei-Chih
authors.identifier: 0000-0003-2401-6536
authors.initials: WC
authors.lastname: Kan
authors.affiliation: Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Yii-Her
authors.initials: YH
authors.lastname: Chou
authors.affiliation: Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Siou-Jin
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: Department of Clinical Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hsu
authors.affiliation: Department of Clinical Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Hsing-Fang
authors.initials: HF
authors.lastname: Lu
authors.affiliation: Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
authors.forename: Wenli
authors.initials: W
authors.lastname: Hsu
authors.affiliation: Department of Clinical Pharmacy, Taipei Medical University, Taipei 110, Taiwan ; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan ; Department of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan ; Department of Pharmacy, Taipei Medical University, Wanfang Hospital, Taipei 116, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D053040:Nephrolithiasis / Q000453:epidemiology* / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase