Levy Nina S, Levy Andrew P
Department of Anatomy, Bruce Rappaport Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
Rambam Maimonides Med J. 2011 Apr 30;2(2):e0047. doi: 10.5041/RMMJ.10047. Print 2011 Apr.
Research over the past 10 years in our laboratory has led to two major findings. The first is that haptoglobin (Hp) genotype can predict the risk of developing vascular complications in individuals with diabetes mellitus (DM), and the second, more far-reaching discovery, is that vitamin E treatment can significantly reduce vascular complications in individuals with DM and the Hp 2-2 genotype. The former finding has been well documented in numerous studies which included over 50,000 patients of diverse geographical and ethnic backgrounds. The latter discovery is more recent and less well accepted by the medical community due to confounding reports over the past 30 years regarding the efficacy of vitamin E treatment for vascular disease. We propose that the benefit of vitamin E treatment was not obvious in earlier studies due to the absence of any genetic basis for patient selection. Our studies dividing DM individuals into vitamin E treatment subgroups based on Hp genotype show a clear benefit for individuals of the Hp 2-2 genotype, while patients carrying the other two Hp genotypes are not affected or may be adversely affected by receiving vitamin E. These findings may explain the overall lack of benefit seen in previous vitamin E studies and emphasize the importance of carefully selecting which patients should receive vitamin E therapy. The pharmacogenomic paradigm discussed in this review potentially could result in a dramatic improvement in the health of millions of individuals worldwide using a treatment that is both accessible and affordable to all.
过去10年我们实验室的研究有两项重大发现。其一，触珠蛋白（Hp）基因型可预测糖尿病（DM）患者发生血管并发症的风险；其二，更具深远意义的发现是，维生素E治疗可显著降低DM且Hp 2-2基因型患者的血管并发症。前一项发现在众多研究中已有充分记录，这些研究纳入了超过50000名来自不同地理和种族背景的患者。后一项发现较新，且由于过去30年关于维生素E治疗血管疾病疗效的相互矛盾的报告，医学界对此接受度较低。我们认为，早期研究中维生素E治疗的益处不明显是因为缺乏患者选择的遗传依据。我们基于Hp基因型将DM患者分为维生素E治疗亚组的研究表明，Hp 2-2基因型个体明显受益，而携带其他两种Hp基因型的患者接受维生素E治疗则无影响或可能受到不利影响。这些发现可能解释了以往维生素E研究中总体未见益处的情况，并强调了仔细选择哪些患者应接受维生素E治疗的重要性。本综述中讨论的药物基因组学模式可能会使全球数百万个体的健康状况得到显著改善，采用的是一种所有人都能获得且负担得起的治疗方法。
