美科学家发现基因变异影响血液凝固

一项最新研究发现：影响血液凝固的基因发生变异，或许能够说明为何医生很难确定华法令的合适剂量，该药是一种常见的抗凝剂。

医生开出处方使用华法令（商品名包括Coumadin）来预防心脏病、脑卒中、或者大手术之后的有害的血液凝固。但是，合适的剂量范围很大，很难进行预测。美国华盛顿大学医学化学教授、高级发起人Allan E. Rettie博士指出：“在过多与过少之间的剂量窗口极小。”

研究人员检测了服用华法令患者的基因背景，发现编码CY2C9酶的基因出现变异，该酶负责华法令的新陈代谢，导致10%的患者对该药的治疗反应不同。医生并不常规检测这些基因的变异。研究人员着眼于另外一种基因：维生素K环氧化物还原酶(VKORC1)，该基因编码的蛋白有助于控制血液凝结，是华法令的关键的作用靶点。研究人员发现，变异并没有基因上调或者下调，因此关于患者变异的信息能够预测对华法令治疗的反应。除此之外，研究人员发现，特定人群特定变异的发生率较高。亚洲裔美国人一般为低剂量背景，非洲裔美国人一般为高剂量背景，欧洲裔美国人则处于中间水平。

第一作者Mark J. Rieder博士指出：“如果你试图预测剂量，你需要知道更多的控制变异的基因。” 他是华盛顿大学基因科学系助理教授。这项研究发表在2005年6月2日的《新英格兰医学》。
 
Genetic Variation Affects Clotting
 
A new study has found that variations in a gene involved in blood clotting may account for the difficulty doctors have in deciding on the proper dose of warfarin, a common anticoagulant.

Warfarin (trade names include Coumadin) is prescribed by doctors to prevent harmful blood clotting after a heart attack, stroke, or major surgery. However, the proper dose can vary a lot and be hard to predict. “There is a narrow window between too much and too little,” explained senior author Allan E. Rettie, Ph.D., professor of medicinal chemistry at the University of Washington (Seattle, USA).

Researchers looked at the genetic background of people taking warfarin and found that variations in the gene encoding the CY2C9 enzyme that metabolizes warfarin account for about 10% of the difference in people’s response to the drug. Doctors do not routinely test for these variations. The researchers also focused on another gene: vitamin K epoxide reductase (VKORC1), which makes a protein that helps control clotting and is the key target of warfarin. They found that genetic variations did turn this gene up or down, so information about a patients’ variations could predict their response to warfarin. In addition, the researchers found that certain population groups tend to have a higher prevalence of a particular variation. Asian Americans tend to have a low-dose version, African-Americans have a high-dose version, and European Americans are in the middle.

“If you want to predict doses, you need to know more about the genes that control variability,” observed first author Mark J. Rieder, Ph.D., an assistant professor in the department of genome sciences at the University of Washington. The study was published in the June 2, 2005, issue of The New England Journal of Medicine.