Sadananda Adiga M N, Chandy S, Ramachandra N, Appaji L, Aruna Kumari B S, Ramaswamy G, Savithri H S, Krishnamoorthy L
Department of Biochemistry, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore-560 029, India.
Indian J Cancer. 2010 Jan-Mar;47(1):40-5. doi: 10.4103/0019-509X.58858.
Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children.
Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A-->C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48-2.45, p = 0.851) and OR for A1298C was 1.29 (95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p = 0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58-6.52, p = 0.286).
The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C-->T and 1298 A-->C gene polymorphisms and risk of ALL, which may be due to the small sample size.
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的一种关键酶，参与DNA合成、DNA修复和DNA甲基化。已表明该酶的基因多态性会影响包括癌症在内的多种疾病。白血病是由对DNA合成有大量需求的快速增殖造血细胞引起的恶性肿瘤。本病例对照研究旨在分析MTHFR基因多态性677C>T和1298A>C与儿童急性淋巴细胞白血病风险之间的关联。
本研究选取了86例确诊为急性淋巴细胞白血病（ALL）的15岁以下患者和99例匹配对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对多态性进行分析。
对照组中MTHFR 677CC和CT的频率分别为85.9%和14.1%，病例组中分别为84.9%和15.1%。病例组和对照组中'T'等位基因频率分别为7%和7.5%。对照组中MTHFR 1298AA、AC和CC的频率分别为28.3%、55.6%和16.1%，病例组中分别为23.3%、59.3%和17.4%。1298A>C的'C'等位基因频率在对照组和病例组中分别为43.9%和47%。C677T的比值比（OR）为1.08（95%CI 0.48 - 2.45，p = 0.851），A1298C的OR为1.29（95%CI 0.65 - 2.29，p = 0.46），1298CC的OR为1.31（95%CI 0.53 - 3.26，p = 0.56）。联合杂合状态（677CT和1298AC）的OR为1.94（95%CI 0.58 - 6.52，p = 0.286）。
在所研究人群中，677MTHFR多态性的'T'等位基因患病率较低。MTHFR 677C>T和1298A>C基因多态性与ALL风险之间无关联，这可能是由于样本量较小。
