ABSTRACT
Objective To research the effect of GGCX gene on MMP13 in rabbit osteoarthritis cartilage cells and investigate its effect on osteoarthritis cartilage degeneration.Methods Six Japanese big ear rabbits weighted (2.0±0.2)kg were randomly di vided into three groups,each group seted a rabbit as control.Anterior cruciate ligament transection method was used to build osteoarthritis cartilage degeneration model at second,forth,sixth week.Articular cartilage was separated successfully after the model were built,cartilage cells were divided from articular cartilage and cultured in 6-well cell culture plate.Cartilage cells were divided into blank group,negative control group and transfection group.PCR method and Western blot were conducted to detect GGCX and MMP13 expressed at the level of mRNA and protein.Results Compare with blank group and negative control group,the expressin level of GGCX incresed,while the MMP13 expression level dcresed(P＜0.05).Conclusion Over expression of GGCX gene can ob viously decrease the expression of MMP13,it provide experimental basis for osteoarthritis of the in vitro gene therapy.
ABSTRACT
Background & objectives: CYP4F2 and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of coumarinic oral anticoagulants (COAs). CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese populations. India has a large population with multiple ethnic groups but there are no reports about the frequencies of these polymorphisms in north Indians. In the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms in a north Indian population and relate these to daily maintenance drug dose requirements of COA. Methods: CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms were genotyped by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) protocols and Taqman SNP discrimination assays in healthy volunteers (n=102) and patients (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve replacement surgery. Results: In healthy volunteers, the allele frequencies for CYP4F2 1347 G>A and GGCX 12970 C>G were 43.14 and 1.43 per cent, respectively. No significant differences in mean weight normalized doses of acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic regression analysis revealed no significant association of any of the genotypes or alleles with the dosing phenotypes for both the SNPs. Interpretation & conclusions: We report distinct frequencies of CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms in north Indians but these polymorphisms did not have significant bearing on maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients.