亚甲基四氢叶酸还原酶C677T基因多态性及同型半胱氨酸水平与急性淋巴细胞白血病患者血栓发生风险的相关性分析

Correlation analysis of methylenetetrahydrofolate reductase C677T gene polymorphism and homocysteine level with the risk of thrombosis in patients with acute lymphoblastic leukemia

目的探讨亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性及同型半胱氨酸(Hcy)水平与急性淋巴细胞白血病(ALL)患者血栓发生风险的相关性。方法选择2019年1月至2020年4月于河北北方学院附属第一医院就诊的ALL患者140例,其中发生静脉血栓者43例,未发生者97例。患者入院时均测定血清同型半胱氨酸(Hcy)水平,并分析MTHFR C677T基因多态性。收集患者临床基线资料及实验室检查资料,并进行倾向性评分匹配后采用Logistic回归分析评价MTHFR C677T基因多态性及Hcy与患者血栓发生之间的关系。结果倾向性评分匹配后,发生血栓组患者纤维蛋白原、D-二聚体、纤维蛋白原降解产物及Hcy水平均显著高于未发生血栓组[(0.94±0.21)g/L比(0.86±0.19)g/L、(0.41±0.09)mg/L比(0.37±0.07)mg/L、(2.1±0.7)mg/L比(1.9±0.5)mg/L、(15±6)μmol/L比(13±4)μmol/L](均P<0.05),2组患者MTHFR C677T基因多态性分布及CT基因型频率差异均有统计学意义(均P<0.05)。Logistic回归分析结果显示,Hcy(比值比=1.217,95%置信区间:1.063~1.393,P=0.005)为影响血栓发生的危险因素;MTHFR C677T基因多态性为血栓发生的独立影响因素(比值比=7.857,P=0.022),其中与TT基因型比较,CC基因型为影响血栓发生的保护因素(比值比=0.092,95%置信区间:0.017~0.493,P=0.005)。结论MTHFR C677T基因多态性及Hcy水平均与ALL患者血栓发生显著相关。

Objective To investigate the association between methylenetetrahydrofolate reductase(MTHFR) C677T gene polymorphism,homocysteine(Hcy)level and thrombocytic risk in patients with acute lymphoblastic leukemia(ALL).Methods From January 2019 to April 2020,140 patients with ALL who were treated in the First Affiliated Hospital of Hebei North University were selected,including 43 patients with venous thrombosis and 97 patients without thrombosis.The serum homocysteine(Hcy)levels were measured when the patients were admitted to the hospital,and the MTHFR C677T gene polymorphism was analyzed.The clinical baseline data and laboratory examination data of patients were collected.After matching the propensity scores,Logistic regression analysis was used to evaluate the relationship between polymorphism of MTHFR C677T gene,Hcy and thrombosis.Results After the propensity score matching,fibrinogen,D-dimer,fibrinogen degradation products and Hcy levels in the thrombosis group were significantly higher than those in the non-thrombosis group[(0.94±0.21)g/L vs(0.86±0.19)g/L,(0.41±0.09)mg/L vs(0.37±0.07)mg/L,(2.1±0.7)mg/L vs(1.9±0.5)mg/L,(15±6)μmol/L vs(13±4)μmol/L](all P<0.05).There were significant differences in the distribution of MTHFR C677T gene polymorphism and CT genotype frequency between the two groups(both P<0.05).Hcy(odds ratio=1.217,95%confidence interval:1.063-1.393,P=0.005)was an independent risk factor affecting thrombosis.MTHFR C677T gene polymorphism(odds ratio=7.857,P=0.022)was an independent affecting factor of thrombosis,of which CC genotype(odds ratio=0.092,95%confidence interval:0.017-0.493,P=0.005)was a protective factor affecting thrombosis compared with TT genotype.Conclusion The MTHFR C677T gene polymorphism and Hcy level are significantly correlated with ALL.