自身免疫性疾病患者检测PAI-1(4G/5G),ABCB1(3435T>C)在预防甲强龙治疗发生股骨头坏死风险的应用
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摘要
目的检测化学药物甲强龙的耐药位点PAI-1(4G/5G)和ABCB1(3435T>C),为使用甲强龙治疗的患者提供精准的用药指导,避免股骨头坏死风险的发生。方法收集94例血液样本,使用荧光探针原位杂交技术对甲强龙耐药位点PAI-1(4G/5G)和ABCB1(3435T>C)进行检测和分析,评估不同患者甲强龙药物使用的可行性。结果 94例患者中,PAI-1(4G/5G)位点检测结果5G5G(野生型)的患者20例(21.28%),检测结果4G5G(杂合突变型)的患者43例(45.74%),检测结果4G4G(纯合突变型)的患者31例(32.98%);ABCB1(3435T>C)位点检测结果TT(野生型)的患者17例(18.09%),检测结果TC(杂合突变型)的患者44例(46.81%),检测结果CC(纯合突变型)的患者33例(35.10%)。12.77%的患者进行激素甲强龙冲击治疗时引起股骨头坏死的风险为低风险,60.63%的患者进行激素甲强龙冲击治疗时引起股骨头坏死的风险为中等风险,26.60%的患者进行激素甲强龙冲击治疗时引起股骨头坏死的风险是高风险。使用卡方检验,激素甲强龙化学药物两个耐药位点间检测结果对于评估股骨头坏死的风险度没有差异。结论在进行糖皮质激素甲强龙冲击治疗前给患者作甲强龙化学药物耐药基因检测,根据检测结果精准用药,可以使26.59%的患者避免股骨头坏死风险的出现,为患者提供安全的用药指导。
Objective To detect the genes of hormone methylprednisolone for the patients who used glucocorticoid therapy and provide them with accurate guidelines to avoid the occurrence of femoral head necrosis.Methods Collected 94 cases and detected the PAI-1(4 G/5 G) and ABCB1(3435 T>C) of glucocorticoid methylprednisolone using fluorescent dye solution in situ hybridization specificity probe position,analyzed the test results of genetic loci,and evaluated different patients use different dose of hormone methylprednisolone.Results The cases of 5 G5 G of PAI-1(4 G/5 G) were 20(21.28%),the cases of 4 G5 G of PAI-1(4 G/5 G) were 43(45.74%) and the cases of 4 G4 G of PAI-1(4 G/5 G) were 31(32.98%).The cases of TT of ABCB1(3435 t>C) were 17(18.09%),the cases of TC of ABCB1(3435 t>C) were 44(46.81%),the cases of CC of ABCB1(3435 t>C) were 33(35.10%).12.77% of the patients with hormone methylprednisolone shock treatment caused the risk of femoral head necrosis was low risk,60.63% of the patients with hormone methylprednisolone impact caused the risk of femoral head necrosis as medium risk treatment,and 26.60% of the patients with hormone treatment cause the risk was high risk of femoral head necrosis.Conclusion Before glucocorticoids impact methylprednisolone therapy for patients with methylprednisolone genetic testing,which can guide accurate drug use.Such,26.59% of the patients would avoid the risk of femoral head necrosis,and this also provide safe medication guide for other patients.
Objective To detect the genes of hormone methylprednisolone for the patients who used glucocorticoid therapy and provide them with accurate guidelines to avoid the occurrence of femoral head necrosis.Methods Collected 94 cases and detected the PAI-1(4 G/5 G) and ABCB1(3435 T>C) of glucocorticoid methylprednisolone using fluorescent dye solution in situ hybridization specificity probe position,analyzed the test results of genetic loci,and evaluated different patients use different dose of hormone methylprednisolone.Results The cases of 5 G5 G of PAI-1(4 G/5 G) were 20(21.28%),the cases of 4 G5 G of PAI-1(4 G/5 G) were 43(45.74%) and the cases of 4 G4 G of PAI-1(4 G/5 G) were 31(32.98%).The cases of TT of ABCB1(3435 t>C) were 17(18.09%),the cases of TC of ABCB1(3435 t>C) were 44(46.81%),the cases of CC of ABCB1(3435 t>C) were 33(35.10%).12.77% of the patients with hormone methylprednisolone shock treatment caused the risk of femoral head necrosis was low risk,60.63% of the patients with hormone methylprednisolone impact caused the risk of femoral head necrosis as medium risk treatment,and 26.60% of the patients with hormone treatment cause the risk was high risk of femoral head necrosis.Conclusion Before glucocorticoids impact methylprednisolone therapy for patients with methylprednisolone genetic testing,which can guide accurate drug use.Such,26.59% of the patients would avoid the risk of femoral head necrosis,and this also provide safe medication guide for other patients.
引文
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[6] NAITO T,MINO Y,AOKI Y,et al.ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affect renal function in patients with rheumatoid arthritis[J].Clin Chim Acta,2015,455:79-84.
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[8] VAUGHAN D E .PAI-1 and atherothrombosis[J].Journal Thromb Haemost,2005,3(8):1879-1883.
[9] BJORKMAN A,SVENSSON P J,HILLARP A,et al.Factor V leiden and prothrombin gene mutation:risk factors for osteonecrosis of the femoral head in adults[J].Clin Orthop Relat Res,2004,425:168-172.
[10] ASANO T,TAKAHASHI K A,FUJIOKA M,et al.Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects[J].Transplantation,2004,77(2):220-225.
[11] CROWE A,TAN A M.Oral and inhaled corticosteroids:differences in P-glycoprotein(ABCB1) mediated efflux[J].Toxicol Appl Pharmacol,2012,260(3):294-302.
[12] GONG Lili,FANG Lianhua,WANG Heyao,et al.Genetic risk factors for glucocorticoid-induced osteonecrosis:a meta-analysis[J].Steroids,2013,78(4):401-408.
[13] 杨晶,张爱玲,鲁憬莉,等.ABCB1基因多态性与糖皮质激素性股骨头坏死相关性的Meta分析[J].中国医院药学杂志,2016,36(9):732-737.YANG Jing,ZHANG Ailing,LU Jingli,et al.Correlation between ABCB1C3435T and G2677T/A polymorphism and steroid induced osteone cross of femoral head:A Meta analysis[J].Chinese Journal of Hospital Pharmacy,2016,36(9):732-737.
[2] 茅新蕾,韩丽雅,黄向东,等.纤溶酶原激活物抑制物-1基因4G/5G位点多态性与脑梗死的相关性研究[J].现代实用医学,2016,28(8):988-989,1008.MAO Xinlei,HAN Liya,HUANG Xiangdong,et al.The relationship of plasminogen activator inhibitor-i gene 4G/5G polymorphism and cerebral infarction[J].Modern Practical Medicine,2016,28(8):988-989,1008.
[3] GIURGEA G A,BRUNNERZIEGLER S,JILMA B,et al.Plasminogen activator inhibitor-1 4G/5G genotype and residual venous occlusion following acute unprovoked deep vein thrombosis of the lower limb:A prospective cohort study[J].Thrombosis Research,2017,153:71-75.
[4] KIM Hyeok,CHO Changhoon,CHO Yoonje,et al.Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head[J].BMC Musculoskeletal Disorders,2011,12:160-167.
[5] ZENG Zheng,WANG Bing,DAN Haitao,et al.Relation between osteonecrosis of the femoral head and PAI-1 4G/5G gene polymorphism:a meta-analysis[J].International Journal of Clinical and Experimental Medicine,2015,8(11):20337-20342.
[6] NAITO T,MINO Y,AOKI Y,et al.ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affect renal function in patients with rheumatoid arthritis[J].Clin Chim Acta,2015,455:79-84.
[7] KATHIRESAN S,GABRIEL S B,YANG Q,et al.Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels[J].Circulation,2005,112(12):1728-1735.
[8] VAUGHAN D E .PAI-1 and atherothrombosis[J].Journal Thromb Haemost,2005,3(8):1879-1883.
[9] BJORKMAN A,SVENSSON P J,HILLARP A,et al.Factor V leiden and prothrombin gene mutation:risk factors for osteonecrosis of the femoral head in adults[J].Clin Orthop Relat Res,2004,425:168-172.
[10] ASANO T,TAKAHASHI K A,FUJIOKA M,et al.Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects[J].Transplantation,2004,77(2):220-225.
[11] CROWE A,TAN A M.Oral and inhaled corticosteroids:differences in P-glycoprotein(ABCB1) mediated efflux[J].Toxicol Appl Pharmacol,2012,260(3):294-302.
[12] GONG Lili,FANG Lianhua,WANG Heyao,et al.Genetic risk factors for glucocorticoid-induced osteonecrosis:a meta-analysis[J].Steroids,2013,78(4):401-408.
[13] 杨晶,张爱玲,鲁憬莉,等.ABCB1基因多态性与糖皮质激素性股骨头坏死相关性的Meta分析[J].中国医院药学杂志,2016,36(9):732-737.YANG Jing,ZHANG Ailing,LU Jingli,et al.Correlation between ABCB1C3435T and G2677T/A polymorphism and steroid induced osteone cross of femoral head:A Meta analysis[J].Chinese Journal of Hospital Pharmacy,2016,36(9):732-737.