Bradshaw Gabrielle, Sutherland Heidi G, Camilleri Emily T, Lea Rodney A, Haupt Larisa M, Griffiths Lyn R
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane QLD, Australia.
Meta Gene. 2015 Oct 22;6:91-5. doi: 10.1016/j.mgene.2015.09.004. eCollection 2015 Dec.
The methylenetetrahydrofolate reductase (MTHFR) gene codes for the MTHFR enzyme which plays a key role in the pathway of folate and methionine metabolism. Polymorphisms of genes in this pathway affect its regulation and have been linked to lymphoma. In this study we examined whether we could detect an association between two common non-synonymous MTHFR polymorphisms, 677C > T (rs1801133) and 1298A > C (rs1801131), and susceptibility to non-Hodgkin lymphoma (NHL) in an Australian case-control cohort. We found no significant differences between genotype or allele frequencies for either polymorphisms between lymphoma cases and controls. We also explored whether epigenetic modification of MTHFR, specifically DNA methylation of a CpG island in the MTHFR promoter region, is associated with NHL using blood samples from patients. No difference in methylation levels was detected between the case and control samples suggesting that although hypermethylation of MTHFR has been reported in tumour tissues, particularly in the diffuse large B-cell lymphoma subtype of NHL, methylation of this MTHFR promoter CpG island is not a suitable epigenetic biomarker for NHL diagnosis or prognosis in peripheral blood samples. Further studies into epigenetic variants could focus on genes that are robustly associated with NHL susceptibility.
亚甲基四氢叶酸还原酶（MTHFR）基因编码MTHFR酶，该酶在叶酸和蛋氨酸代谢途径中起关键作用。此途径中基因的多态性会影响其调控，并与淋巴瘤相关。在本研究中，我们检测了澳大利亚病例对照队列中两种常见的非同义MTHFR多态性，即677C>T（rs1801133）和1298A>C（rs1801131），与非霍奇金淋巴瘤（NHL）易感性之间是否存在关联。我们发现淋巴瘤病例与对照之间，这两种多态性的基因型或等位基因频率均无显著差异。我们还利用患者的血液样本，探讨了MTHFR的表观遗传修饰，特别是MTHFR启动子区域CpG岛的DNA甲基化，是否与NHL相关。病例样本与对照样本之间未检测到甲基化水平的差异，这表明尽管在肿瘤组织中，特别是在NHL的弥漫性大B细胞淋巴瘤亚型中，已报道MTHFR存在高甲基化，但该MTHFR启动子CpG岛的甲基化并非外周血样本中NHL诊断或预后的合适表观遗传生物标志物。对表观遗传变异的进一步研究可聚焦于与NHL易感性密切相关的基因。
