Genetic mutation of vitamin K-dependent gamma-glutamyl carboxylase domain in patients with calcium oxalate urolithiasis

Abstract

To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalate urolithasis, renal cortex and peripheral blood samples were obtained from severe hydronephrosis patients (with or without calculi), and renal tumor patients undergoing nephrectomy. GGCX mutations in all 15 exons were examined in 44 patients with calcium oxalate urolithiasis (COU) by polymerase chain reaction (PCR) and denatured high pressure liquid chromatography (DHPLC), and confirmed by sequencing. Mutation was not found in all COU samples compared to the controls. These data demonstrated that functional GGCX mutations in all 15 exons do not occur in most COU patients. It was suggested that there may be no significant association between the low activity and mutation of GGCX in COU.

Keywords

calcium oxalate / urinary calculi / vitamin K-dependent gamma-glutamyl carboxylase / mutation / denatured high pressure liquid chromatography

References

[1] WattsR.W.. Idiopathic urinary stone disease: possible polygenic aetiological factors. QJM, 2005, 98(4): 241-246

[2] StapletonA.M., RyallR.L.. Blood coagulation proteins and urolithiasis are linked: crystal matrix protein is the F1 activation peptide of human prothrombin. Br J Urol, 1995, 75(6): 712-719

[3] GroverP.K., RyallR.L.. Inhibition of calcium oxalate crystal growth and aggregation by prothrombin and its fragments in vitro: relationship between protein structure and inhibitory activity. Eur J Biochem, 1999, 263(1): 50-56

[4] LiuJ.H., WangT., ChenJ.H., et al.. Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its gamma-carboxyglutamic acid residues. Urology, 2006, 67(1): 201-203

[5] FurieB., BouchardB.A., FurieB.C.. Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood, 1999, 93(6): 1798-1808

[6] ChenJ.H., LiuJ.H., ZhangY.S., et al.. Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in calcium oxalate calculi patients. Chin Med J (Engl), 2003, 116(4): 569-572

[7] WolfordJ.K., BluntD., BallecerC., et al.. High-throughput SNP detection by using DNA pooling and denaturing high performance liquid chromatography (DHPLC). Hum Genet, 2000, 107(5): 483-487

[8] OldenburgJ., von BrederlowB., FreginA., et al.. Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex. Thromb Haemost, 2000, 84(6): 937-941

[9] KuoW.L., StaffordD.W., CrucesJ., et al.. Chromosomal localization of the gamma-glutamyl carboxylase gene at 2p12. Genomic, 1995, 25(3): 746-748

[10] WuS.M., StaffordD.W., FrazierD., et al.. Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase. Blood, 1997, 89(11): 4058-4062

[11] WuS.M., CheungW.F., FrazierD., et al.. Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science, 1991, 254(5038): 1634-1636

[12] RomeroE.E., Velazquez-EL.J., DeoR., et al.. Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos. Expe Cell Rech, 1998, 243(2): 334-346

[13] FriedmanP.A., MitchW.E., SilvaP.. Localization of renal vitamin K-dependent gamma-glutamyl carboxylase to tubule cells. J Biol Chem, 1982, 257: 11 037-11 040

[14] BerknerK.L., McNallyB.A.. Purification of vitamin K-dependent carboxylase from cultured cells. Methods Enzymol, 1997, 282(18): 313-333

[15] LeslieY.C., NiclasE., RhianG., et al.. Gamma-glutamyl carboylase (GGCX) microsatellite and warfarin dosing. Blood, 2005, 106(10): 3673-3674

[16] HiroyukiK., KimieN., KeinichiroN., et al.. An functional single nucleotide polymorphism in the vitamin-K-dependent gamma-glutamyl carboxylase gene (Arg 325Gln) is associated with bone mineral density in elderly Japanese women. Bone, 2007, 40(2): 451-456

[17] SpronkH.M., FarahR.A., BuchananG.R., et al.. Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors. Blood, 2000, 96(10): 3650-3652

[18] RostS., GeisenC., FreginA., et al.. Founder mutation Arg485Pro led to recurrent compound heterozygous GGCX genotypes in two German patients with VKCFD type 1. Blood Coagul Fibrinolysis, 2006, 17(6): 503-507

[19] AngayarkanniN., SelvamR.. Enhanced renal vitamin K-dependent gamma-glutamyl carboxylase activity in experimental rat urolithiasis. Eur Urol, 1998, 33(1): 116-120