据channelnewsasia网站2006年8月28日报道，新加坡医生解开了一个迷题，即为什么印度、中国和马来西亚病人使用普通抗血液凝结的华法令阻凝剂时，为了获得同样的效果使用的药物剂量却不相同。此项迷题的解开使未来依据种族开处方药成为可能。
新加坡国立大学医院（NUH）研究小组跟踪一种决定印度病人华法令阻凝剂药物使用量比中国和马来西亚病人多约60%至70%。这是他们成功揭开存在数十年之久遗传秘密的关键。这项研究成果将使数千病人受益。
研究人员正在对癌症病人化疗药物进行类似研究。新加坡国立大学医院血液与肿瘤学系高级顾问古奔成博士是此项研究的领军人，他说，“我们一直对不同种族间药物表现的差异性非常感兴趣”。
华法令阻凝剂广泛地被包括整形外科专科医生、心脏病医生、外科医生和妇科医生在内的许多医生所使用。古博士说，“华法令阻凝剂药物使用所面临的一个问题就是，如果你用量过多就会导致病人流血过多死亡。但是如果用量过少，血液凝块却又会继续存在。药物使用量必须非常严格。以前在使用此种药物之前必须进行血液测试，以决定稀释血液所需用的量”。
现在医院要花费三周实验室测试时间来确定病人华法令阻凝剂药物的需用量。但是在我们发现决定华法令阻凝剂药物剂量的基因后，我们可能会很快解决病人药物用量问题。
研究小组另一名顾问李苏秦博士告诉《今日》称，在去年为期2个多月的研究中，新加坡国立大学医院的研究小组发现这种反复利用体内维生素K的基因，这种基因是华法令阻凝剂在抗凝结过程中攻击的目标。
此项研究的对象是275名中国、马来西亚和印度病人，他们父母和祖父母同样来自相同种族。古博士认为中国人和印度人的祖先绝大多数都是来自各自国家的南部地区。研究发现种族不同，这种基因结构也不相同。这就意味着印度人一天华法令阻凝剂的需求量为6mg，而中国人需求量为3.5mg，马来西亚人的需求量介于印度人和中国人之间。
古博士补充到，一个混血人可能具有“介于中间的”遗传基因结构，因此他可能就会需要一个介于中间的华法令阻凝剂药物剂量。
此项研究成果刊登在1月份的《临床药理学和治疗学》杂志上。该杂志是一个国际知名的同行评审杂志。鉴于此项研究具有重要的临床应用意义和短期投入应用的前景，新加坡国立大学医院将很快实施另一项计划，即在自愿者病人身上验证此项研究发现。
如果得到确认，华法令阻凝剂可能就会成为全球首种能根据病人父母种族来决定处方药剂量的药物。新加坡国立大学医院同时正着手对另外10种药物进行研究，这10药物大部分为化疗药物，以论证不同种族对这些药物的反应差异。古博士说，“目前我们都是依据西方研究成果来开处方”。西方最近研究显示白种人可能在药物剂量的需求上要比非白种人更高。假如病人出现药物副作用反应我们应当如何应对呢？他表示，尽管减少药物剂量与最初使用药物剂量一样具有引发致命后果的可能性，但是我们所采取的首要一步还是要在后续治疗中减少药物剂量。
古博士称，新加坡医生在为病人开化疗药物剂量时，医生经常不得不对约20%至30%的病人药物剂量进行修正。
疫苗——癌症病人的福音
一种针对一些最严重癌症的新疫苗可以防止病人在首次外科手术或者药物治疗后出现复发。一个对来自英国和其它欧盟国家的700名肾癌病人进行治疗的计划将在今年内起动。过去的经验显示这种治疗是安全的，它通过激发人体自身的免疫系统来攻击肿瘤。
直肠癌和乳腺癌同样也被列入该疫苗临床验证的计划之中。明年一种名为Gardasil的能预防妇女子宫癌的新疫苗同时也有可能会面市。伦敦南区ST乔治医院的肿瘤教授格斯·达尔格里斯博士帮助开发出了一种能有效预防前列腺癌的疫苗，该疫苗目前正在英国全国范围内进行大规模试验。
英文原文：
NUH team discovers how gene affects drug dosage
Singapore doctors have solved the puzzle of why Indian, Chinese and Malay patients need different dosages of the commonly-used anti-clotting drug - warfarin - to achieve the same effect, raising the possibility that medicine, in the future, could be prescribed based on ethnicity.
The key to solving the decades-old mystery is genetics, and research by a National University Hospital (NUH) team has tracked down a gene which determines why Indians need about 60 to 70 per cent more warfarin than their Chinese and Malay counterparts.
This knowledge can benefit thousands of patients.
Similar studies are being carried out on drugs being used in chemotherapeutic treatment of cancer patients.
"That drug behaviour is different between races is something we have always been very interested in," said senior consultant of NUH's haematology-oncology department, Dr Goh Boon Cher, the leader of the research team.
And that is the case with warfarin which is widely used by doctors, including orthopaedic specialists, cardiologists, surgeons and gynaecologists.
"The problem with this drug is that if you give too much the patient will bleed to death," explained Dr Goh.
But if too little is given, the clot persists.
"One has to be very tight with dosage. Previously, after the drug was given, blood tests would be carried out to determine the amount of thinning in the blood," said Dr Goh.
Currently, hospitals take three weeks of laboratory work to establish how much warfarin a patient needs.
But the discovery that a gene decides the matter may soon put the issue at rest.
In its study, conducted over two months last year, the NUH team found that this gene recycles the body's Vitamin K, which is the target of warfarin in the anti-clotting process, consultant Dr Lee Soo Chin, another member of the team, told Today.
The study focused on 275 people in the Chinese, Malay and Indian ethnic groups as indicated by their Identity Cards, and whose parents and grandparents were also from the same ethnic group.
Dr Goh noted that the forefathers of the Chinese and Indian subjects were mostly from the south of both countries.
The study found that there are variations in the makeup of the gene in different races.
This means that Indians need 6mg a day of warfarin, compared to 3.5mg a day for the Chinese.
Malays need an intermediate dosage.
Dr Goh added that a person with mixed parentage may have "intermediate" genetic makeup and may thus require an intermediate dosage of warfarin.
The study was published in the January issue of the prestigious international peer-reviewed journal, Clinical Pharmacology and Therapeutics.
As the study is clinically significant and has immediate application, NUH will soon embark on another project to validate the findings of the study, this time among volunteer patients.
If validated, warfarin may well be the first drug in the world to be prescribed in dosages based on the patient's ethnic group.
The NUH is also studying some 10 drugs - most of them used in chemotherapy - which the various ethnic groups demonstrate different reactions to.
"Currently, we prescribe according to literature that comes from the West," said Dr Goh. Recent studies conducted in the West show that Caucasian patients may require higher dosages compared to non-Caucasians.
What if the patient shows adverse side-effects? The obvious step would be to reduce the dosage in subsequent treatment, he said, though there is also the possibility that the initial dosage can result in fatal consequences.
Dr Goh added that doctors in Singapore often have to adjust the dosage of chemotherapeutic drugs in 20 to 30 percent of patients.
Vaccine hope for Cancer patients
A new vaccine which targets some of the most serious forms of cancer may prevent patients from suffering a relapse once they have had initial surgery or drugs treatment, the Guardian reported yesterday.
A trial involving 700 patients with kidney cancer will start this year across Britain and other European countries.
The work already done suggests the therapy is safe and that it triggers the body's own immune system to attack the tumour.
Other clinical trials looking at the vaccine's impact on patients with colorectal and breast cancer are also planned.
Also likely to see introduction within the next year is a vaccine, Gardasil, to prevent women developing cervical cancer, while Dr Gus Dalgleish, professor of oncology at St George's Hospital in south London, has helped to develop a vaccine which may prove effective against prostate cancer, and is now embarking on a large-scale randomised trial across the country.
