漢族人群VKORC1啟動(dòng)子基因多態(tài)性與華法林劑量相關(guān)性研究
發(fā)布時(shí)間：2019-01-08 07:27
【摘要】： 目的:探討在漢族人群中VKORC1啟動(dòng)子的基因多態(tài)性與華法林口服劑量關(guān)系。 方法:隨機(jī)患者100例和從近6年在我院行人工機(jī)械瓣膜置換術(shù)后患者中篩查獲得華法林耐藥患者12例。抽取患者外周血,提取患者gDNA,應(yīng)用相關(guān)引物PCR擴(kuò)增,凝膠電泳鑒定擴(kuò)增片段,對(duì)樣本VKORC1啟動(dòng)子進(jìn)行ABI3100序列分析,從而獲得以上兩組患者VKORC1基因多態(tài)性分布。 結(jié)果:在100例隨機(jī)抽樣患者中僅發(fā)現(xiàn)g.-1639 G＞A突變,其基因多態(tài)性分布情況為從型87例(87%),AG型13例(13%),GG型0例(0%);在12例華法林耐藥的特殊患者中也發(fā)現(xiàn)g.-1639 G＞A突變,其基因多態(tài)性分布情況為從型4例(25%),AG型7例(67%),GG型1例(8%)。 結(jié)論:漢族人群中g(shù).-1639G＞A突變極高,而野生純合子極少見,可以解釋漢族人群對(duì)華法林藥物普遍敏感。在12例華法林耐藥漢族患者中存在8例非g.-1639G＞A突變純合子(1例GG型和7例AG型)可能是這些患者華法林耐藥的原因之一,這部分患者在僅加大華法林劑量情況下,達(dá)到理想INR標(biāo)準(zhǔn)。在12例華法林耐藥漢族患者中有4例g.-1639G＞A突變純合子(AA型),這部分患者耐藥與其它因素有關(guān)。
[Abstract]:Objective: to investigate the relationship between VKORC1 promoter gene polymorphism and warfarin oral dose in Han population. Methods: 100 random patients and 12 patients with warfarin resistance were selected from 6 years after valvular replacement in our hospital. The peripheral blood of the patients was extracted and the gDNA, was amplified by PCR with the relevant primers. The amplified fragments were identified by gel electrophoresis, and the ABI3100 sequence of the VKORC1 promoter was analyzed to obtain the distribution of VKORC1 gene polymorphism in the above two groups. Results: only the mutation of g.-1639G > A was found in 100 random sampling patients. The gene polymorphism was found in 87 cases (87%) of), AG type (13 cases) (13% of), GG type 0 cases (0%). In 12 patients with warfarin resistance, the mutation of g -1639G > A was also found, and the gene polymorphism was found in 4 cases (25%), AG, 7 cases, 67%), GG, 1 case (8%). Conclusion: the mutation of g.-1639G > A in Han population is very high, but the wild homozygote is rare, which can explain that the Han population is generally sensitive to warfarin. The presence of non-G 1639G > A mutant homozygotes (1 GG and 7 AG) in 12 warfarin resistant Han patients may be one of the reasons for warfarin resistance. Meet the ideal INR standard. Among the 12 warfarin resistant Han patients, 4 had g-1639G > A mutation homozygote (AA type), which was related to other factors.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R394
本文編號(hào)：2404299
[Abstract]:Objective: to investigate the relationship between VKORC1 promoter gene polymorphism and warfarin oral dose in Han population. Methods: 100 random patients and 12 patients with warfarin resistance were selected from 6 years after valvular replacement in our hospital. The peripheral blood of the patients was extracted and the gDNA, was amplified by PCR with the relevant primers. The amplified fragments were identified by gel electrophoresis, and the ABI3100 sequence of the VKORC1 promoter was analyzed to obtain the distribution of VKORC1 gene polymorphism in the above two groups. Results: only the mutation of g.-1639G > A was found in 100 random sampling patients. The gene polymorphism was found in 87 cases (87%) of), AG type (13 cases) (13% of), GG type 0 cases (0%). In 12 patients with warfarin resistance, the mutation of g -1639G > A was also found, and the gene polymorphism was found in 4 cases (25%), AG, 7 cases, 67%), GG, 1 case (8%). Conclusion: the mutation of g.-1639G > A in Han population is very high, but the wild homozygote is rare, which can explain that the Han population is generally sensitive to warfarin. The presence of non-G 1639G > A mutant homozygotes (1 GG and 7 AG) in 12 warfarin resistant Han patients may be one of the reasons for warfarin resistance. Meet the ideal INR standard. Among the 12 warfarin resistant Han patients, 4 had g-1639G > A mutation homozygote (AA type), which was related to other factors.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R394
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 周國華;單核苷酸多態(tài)性(SNP)與個(gè)體化用藥[J];中國藥學(xué)雜志;2004年02期
，本文編號(hào)：2404299
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