GSTP1、CYP2E1基因遗传多态性与急性白血病易感性的关系

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本研究旨在探讨谷胱甘肽巯基转移酶P1(GSTP1)和细胞色素P4502E1(CYP2E1)基因多态性与急性白血病易感性的关系。采用1∶1配对病例-对照、LDR分型方法对150例急性白血病(AL)患者和150例对照组进行GSTP1和CYP2E1的基因多态性进行检测。结果表明:AL病例组GSTP1基因G等位基因频率(26.7%)和Ile/Val和Val/Val基因型频率(44%)均高于对照组(10%和16%)。携带突变基因型(Ile/Val和Val/Val)个体发生AL的相对风险度为Ile/Ile个体的3.226倍(95%CI=1.527-5.236)。进一步分层分析表明,急性髓系白血病(AML)病例组Ile/Val和Val/Val基因型频率(55.0%)高于对照组(16%)(p<0.05)。携带Ile/Val和Val/Val基因型的个体发生AML的相对风险度为野生基因型(Ile/Ile)个体的2.214倍(95%CI=1.009-3.260)。AL病例组CYP2E1基因C2等位基因频率(16.7%)和C1C2/C2C2基因型频率(30%)均高于对照组(13.9%和26%),但其差异均无统计学意义。进一步分层分析显示,急性髓系白血病(AML)病例组突变基因型(C1C2/C2C2)频率(36%)高于对照组(32%),其差异无统计学意义。两基因多态交互作用分析显示,GSTP1杂合型和突变型者(Ile/Val+Val/Val)且CYP2E1杂合型和突变型者(C1C2+C2C2)发生AML的风险约增加3.208倍。结论 :GSTP1与急性髓系白血病易感性相关,携带GSTP1突变基因型(Ile/Val+Val/Val)个体可降低白血病的发病风险;CYP2E1与急性白血病易感性无关,GSTP1野生型且CYP2E1杂合型和突变型联合作用可进一步降低AML的发病风险。 This study aimed to investigate the relationship between glutathione S-transferase P1 (GSTP1) and cytochrome P4502E1 (CYP2E1) gene polymorphisms and susceptibility to acute leukemia. The gene polymorphisms of GSTP1 and CYP2E1 were detected in 150 cases of acute leukemia (AL) and 150 cases of control group by 1: 1 paired case-control and LDR classification. The results showed that G allele frequency (26.7%) and Ile / Val and Val / Val genotype frequencies (44%) were significantly higher in AL patients than in controls (10% and 16%). The relative risk of developing AL in individuals carrying the mutated genotypes (Ile / Val and Val / Val) was 3.226-fold (95% CI = 1.527-5.236) for Ile / Ile individuals. Further stratification analysis showed that the frequencies of Ile / Val and Val / Val genotypes (55.0%) were higher in acute myeloid leukemia (AML) cases than in controls (16%) (p <0.05). Individuals carrying the Ile / Val and Val / Val genotypes developed a 2.214-fold (95% CI = 1.009-3.260) relative risk of developing AML for individuals with wild-type (Ile / Ile) individuals. The frequencies of C2 allele (16.7%) and C1C2 / C2C2 (30%) of CYP2E1 gene in AL cases were higher than those in control group (13.9% and 26%), but the differences were not statistically significant. Further stratification analysis showed that the frequency of C1C2 / C2C2 (36%) was higher than that of the control group (32%) in acute myeloid leukemia (AML) cases, the difference was not statistically significant. Polymorphic interaction analysis showed that the risk of AML in heterozygous and mutant GSTP1 (Ile / Val + Val / Val) and CYP2E1 heterozygous and mutant (C1C2 + C2C2) increased about 3.208 fold. Conclusions: GSTP1 is associated with the susceptibility to acute myeloid leukemia. Individuals carrying the GSTP1 mutation genotype (Ile / Val + Val / Val) may reduce the risk of leukemia. CYP2E1 has no relationship with susceptibility to acute leukemia. GSTP1 wild type and CYP2E1 heterozygous Combined with mutation can further reduce the risk of AML.
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