Rao D Nageswara, Manjula G, Sailaja K, Surekha D, Raghunadharao D, Rajappa Senthil, Vishnupriya S
Department of Genetics, Osmania University, Hyderabad, India.
Indian J Hum Genet. 2011 Sep;17(3):175-8. doi: 10.4103/0971-6866.92098.
CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A53). We investigated the association between CYP3A53 polymorphism and acute leukemia.
Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A53 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A53 polymorphism and acute leukemia.
The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ(2)- 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL.
The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.
在急性白血病患者中，CYP3A5被认为是导致个体间CYP3A依赖性药物代谢差异的重要遗传因素。CYP3A5表达缺失主要由6986A>G处的单核苷酸多态性（CYP3A53）引起。我们研究了CYP3A53多态性与急性白血病之间的关联。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对289例急性白血病病例（包括145例急性淋巴细胞白血病、144例急性髓细胞白血病）及241例对照样本进行CYP3A53多态性分析。使用SPSS 15.0版软件进行统计分析，以检测CYP3A53多态性与急性白血病之间的关联。
CYP3A5*3多态性的3/3基因型与急性白血病的发生显著相关（χ² = 133.53；自由度 = 2，P < 0.000）。当对临床变量进行数据分析时，3/3基因型的急性淋巴细胞白血病和急性髓细胞白血病病例的平均白细胞计数、原始细胞百分比和乳酸脱氢酶水平均升高。流行病学变量对急性髓细胞白血病或急性淋巴细胞白血病发生的基因型风险无影响。
结果表明，CYP3A5*3多态性可能会增加患急性淋巴细胞白血病或急性髓细胞白血病的风险，强调了在致癌过程中有效I期解毒的重要性。该多态性与临床变量的关联表明，3/3基因型也可能导致患者生存率较低。
