ABSTRACT
OBJECTIVE: In this study, the relationship between osteoporotic vertebral fractures and 9041 Guanine/Adenine and 3673 Guanine/Adenine polymorphisms related to the vitamin K epoxide reductase complex subunit-1 (VKORC1) gene in postmenopausal women with osteoporosis was investigated. METHOD: DNA was isolated from blood samples collected from 150 women with postmenopausal osteoporosis. Genotyping of the two polymorphic regions (9041 Guanine/Adenine and 3673 Guanine/Adenine) in VKORC1 was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. The presence of radiographic fractures among the 150 patients was ascertained by using the Genant method. RESULT: At least one fracture was detected in 98 patients, and no fracture was observed in 52 patients on radiological images. We found no association between the 9041 Guanine/Adenine (p=0.283) and 3673 Guanine/Adenine (p=0.232) polymorphisms of the VKORC1 gene and the development of secondary postosteoporotic fractures in our study. CONCLUSION: There was no relationship between osteoporotic vertebral fracture and VKORC1 gene polymorphism in a postmenopausal Turkish population.
Subject(s)
Humans , Female , Middle Aged , Aged , Polymorphism, Genetic/genetics , Osteoporosis, Postmenopausal/genetics , Spinal Fractures/genetics , Osteoporotic Fractures/genetics , Vitamin K Epoxide Reductases/genetics , Turkey , Bone Density , Pilot Projects , Retrospective Studies , Genetic Association Studies , Gene Frequency/geneticsABSTRACT
Objective To use the fluorescence PCR‐melting curve method to detect CYP2C9 and VKORC1 gene polymorphism in Xinjiang Hui population ,to analyze their gene distribution and gene mutation frequency ,and to evaluate the clinical applicability of the fluorescence PCR‐melting curve method .Methods The fluorescence PCR‐melting curve method and sequencing method were adopted to contrastively detect CYP2C9*2 ,CYP2C9*3 and VKORC1(‐1639G/A)gene polymorphism .Results Among detected 228 Xinjiang Hui individuals ,199 cases of CYP2C9*1/*1 ,2 cases of CYP2C9*1/*2 ,26 cases of CYP2C9*1/*3 and only 1 case of CYP2C9*3/*3 were detected ,no case of CYP2C9*2/*2 and CYP2C9*2/*3 was detected .Two kinds of allele G and A were detected for VKORC1(‐1639G/A) ,in which VKORC1‐1639G/G type was detected in 2 cases ,VKORC1‐1639G/A type was detected in 39 cases and VKORC1‐1639A/A type was detected in187 cases ,compared with the sequencing method ,the results of the fluorescence PCR‐melting curve method were completely consistent .Conclusion Xinjiang Hui population also has CYP2C9 gene *2 ,*3 loci and VKORC1 gene(‐1639G/A) locus polymorphism ,their occurrence frequency has a certain difference with Xingjiang Uygur and other regional populations ,the adopted fluorescence PCR‐melting curve method used in the gene polymorphism detection can meet clinical detection requirements .
ABSTRACT
Warfarin is still the most clinically used oral anti-coagulant despite of its narrow therapeutic index and high risk of hemorrhage. The mean daily dose of warfarin varies widely from patient to patient, and to achieve the same therapeutic effect, the daily dose of warfarin could be varied over 20-fold. The variability in warfarin dosage depends on several factors, including gene polymorphisms, index of body mass, age and other drugs, and these factors compelled the clinicians to individualize warfarin dosage in order to optimize the therapeutic regimen. A number of genes are involved in metabolism of warfarin, such as cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 4F2 (CYP4F2), gamma-glutamylcarboxylase (GGCX), etc. Of them CYP2C9 and VKORC1 are the emphasis of current researches. The association between the polymorphism of CYP2C9 and VKORC1 and individualized warfarin therapeutic regimen are mainly discussed in this paper.
ABSTRACT
Urinary prothrombin fragment 1 (UPTF1) is a potent inhibitor of urinary stone formation.UPTF1 exerts such inhibitory effect by effective γ-carboxylation in which vitamin K epoxide reductase complex subunit 1 (VKORC1),the rate-limiting enzyme,is involved.This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis.The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups:urolithiasis group,control group A [hydronephrosis-without-stone (HWS) group],control group B (normal control group).The localization and expression of VKORC 1 in renal tissues were determined by using immunohistochemistry,immunofluorescence microscopy,Western blotting and SYBR Green Ⅰreal-time reverse-transcription PCR.The rapid amplification of cDNA ends (RACE) were conducted to obtain the 3'- and 5'-untranslated region (UTR) of VKORC1.The results showed that VKORC1was located in the cytoplasm of renal tubular epithelial cells.The expression of VKORC 1 in the urolithiasis group was significantly lower than that in the other two control groups (P＜0.05).Moreover,the 3'- and 5'-UTR sequence of the VKORC 1 gene was successfully cloned.No insertion or deletion was found in the 3'- and 5'-UTR.However,a 171-bp new base sequence was discovered in the upstream of 5'-UTR end in the urolithiasis group.It was concluded that the decreased expression of VKORC1 may contribute to the development of calcium oxalate urolithiasis in the kidney.