【摘要】：目的研究湖北地區(qū)漢族人性別、年齡、身高、體重、細(xì)胞色素P450酶2C9基因(CYP2C9)和維生素K環(huán)氧化物還原酶復(fù)合體亞單位1(VKORC1)基因型與華法林穩(wěn)態(tài)劑量及計算機模型預(yù)測劑量的相關(guān)性。方法收集湖北地區(qū)漢族人群臨床使用華法林的患者,采用聚合酶鏈反應(yīng)-限制性內(nèi)切酶片段長度多態(tài)性(PCR-RFLP)技術(shù)檢測CYP2C9和VKORC1基因型,同時記錄患者的年齡、性別、體重、身高、國際標(biāo)準(zhǔn)化比值(INR)、華法林穩(wěn)態(tài)劑量和計算機模型預(yù)測劑量等臨床資料,并對這些臨床資料進(jìn)行相關(guān)分析及多元回歸分析。結(jié)果 435例患者的CYP2C9基因型檢測顯示402例為*1/*1型(92.41%)、30例為*1/*3型(6.90%)、3例*3/*3型(0.69%)。前兩型患者華法林劑量分別為(2.91±1.12)mg/d、(1.91±0.85)mg/d,*1/*3型較*1/*1型華法林需求量少,差異有統(tǒng)計學(xué)意義(P0.01)(CYP2C9基因型*3/*3型樣本量太少,未參與組間比較);VKORC1基因型檢測顯示354例為AA型(81.4%)、77例為雜合子GA型(17.7%)、4例為純合子GG型(0.9%)�；颊呷A法林劑量分別為(2.58±0.94)mg/d、(3.82±1.52)mg/d、(5.62±1.77)mg/d,AA型較GA型華法林需求量少,兩組間比較差異有統(tǒng)計學(xué)意義(P0.01)(VKORC1基因型GG型樣本量太少,未參與組間比較)。同時對患者的年齡、身高、體重、兩種基因型、穩(wěn)態(tài)劑量以及計算機模型預(yù)測劑量均分別行相關(guān)分析及多元回歸分析,提示華法林劑量與患者的年齡、身高、體重及不同的基因型均有關(guān),且相關(guān)分析提示計算機模型預(yù)測劑量與穩(wěn)態(tài)劑量的相關(guān)系數(shù)為0.611,且有統(tǒng)計學(xué)意義;行穩(wěn)態(tài)劑量的多元回歸分析顯示CYP2C9、VKORC1基因型、年齡、體重與穩(wěn)態(tài)劑量相關(guān),有統(tǒng)計學(xué)意義。結(jié)論在湖北地區(qū)漢族人群中,存在CYP2C9和VKORC1基因多態(tài)性,且不同基因型患者間華法林用量存在差異,同時華法林劑量與年齡、體重及不同的基因型有關(guān),計算機模型預(yù)測劑量與穩(wěn)態(tài)劑量存在相關(guān)性且有統(tǒng)計學(xué)意義。
[Abstract]:Objective to study the gender, age, height, weight of Han nationality in Hubei province. Correlation of cytochrome P450 enzyme 2C9 gene (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotype with warfarin steady-state dose and predicted dose by computer model. Methods CYP2C9 and VKORC1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients with warfarin. Age, sex, weight, height were recorded. International standardized ratio (INR), warfarin steady-state dose and computer model predicted dose and other clinical data, and these clinical data were analyzed and multivariate regression analysis. Results the CYP2C9 genotypes of 435 patients showed that 402 cases were 1 / 1 type (92.41%) and 30 cases were 1 / 1 / 3 (6.90%) / 3 / 3 (0.69%). The doses of warfarin in the first two types of patients were (2.91 鹵1.12) mg / d, (1.91 鹵0.85) mg / d and (1.91 鹵0.85) mg / d / 3, respectively. The demand for warfarin in the first two types of patients was significantly lower than that in the first type of warfarin (P0.01) (P0.01). VKORC1 genotypes were detected in 354 cases of AA (81.4%) and 77 cases of heterozygote GA (17.7%). 4 cases were homozygous GG (0.9%). The doses of warfarin were (2.58 鹵0.94) mg / d, (3.82 鹵1.52) mg / d, (5.62 鹵1.77) mg / d and (5.62 鹵1.77) mg / d, respectively. The difference between the two groups was statistically significant (P0.01). Age, height, weight, two genotypes, steady-state dose and predicted dose of computer model were analyzed by correlation analysis and multivariate regression analysis, which suggested that warfarin dose was associated with age and height. The correlation coefficient between predicted dose and steady-state dose by computer model was 0.611, and the multivariate regression analysis of steady-state dose showed that CYP2C9 VKORC1 genotype, age, and age were correlated with body weight and genotype. Body weight was significantly correlated with steady dose. Conclusion there are polymorphisms of CYP2C9 and VKORC1 genes in the Han population in Hubei, and the dosage of warfarin is different among different genotypes, and the dosage of warfarin is related to age, body weight and different genotypes. There is a correlation between the predicted dose and the steady-state dose by computer model and there is statistical significance.
【作者單位】： 武漢亞洲心臟病醫(yī)院心外科;
【基金】：武漢市衛(wèi)計委臨床醫(yī)學(xué)科研項目(No.WX13B28)
【分類號】：R969

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