據(jù)channelnewsasia網(wǎng)站2006年8月28日?qǐng)?bào)道，新加坡醫(yī)生解開(kāi)了一個(gè)迷題,，即為什么印度,、中國(guó)和馬來(lái)西亞病人使用普通抗血液凝結(jié)的華法令阻凝劑時(shí)，為了獲得同樣的效果使用的藥物劑量卻不相同,。此項(xiàng)迷題的解開(kāi)使未來(lái)依據(jù)種族開(kāi)處方藥成為可能,。
新加坡國(guó)立大學(xué)醫(yī)院（NUH）研究小組跟蹤一種決定印度病人華法令阻凝劑藥物使用量比中國(guó)和馬來(lái)西亞病人多約60%至70%。這是他們成功揭開(kāi)存在數(shù)十年之久遺傳秘密的關(guān)鍵,。這項(xiàng)研究成果將使數(shù)千病人受益,。
研究人員正在對(duì)癌癥病人化療藥物進(jìn)行類(lèi)似研究。新加坡國(guó)立大學(xué)醫(yī)院血液與腫瘤學(xué)系高級(jí)顧問(wèn)古奔成博士是此項(xiàng)研究的領(lǐng)軍人,，他說(shuō),，“我們一直對(duì)不同種族間藥物表現(xiàn)的差異性非常感興趣”,。
華法令阻凝劑廣泛地被包括整形外科專(zhuān)科醫(yī)生、心臟病醫(yī)生,、外科醫(yī)生和婦科醫(yī)生在內(nèi)的許多醫(yī)生所使用,。古博士說(shuō)，“華法令阻凝劑藥物使用所面臨的一個(gè)問(wèn)題就是,，如果你用量過(guò)多就會(huì)導(dǎo)致病人流血過(guò)多死亡,。但是如果用量過(guò)少，血液凝塊卻又會(huì)繼續(xù)存在,。藥物使用量必須非常嚴(yán)格,。以前在使用此種藥物之前必須進(jìn)行血液測(cè)試，以決定稀釋血液所需用的量”,。
現(xiàn)在醫(yī)院要花費(fèi)三周實(shí)驗(yàn)室測(cè)試時(shí)間來(lái)確定病人華法令阻凝劑藥物的需用量,。但是在我們發(fā)現(xiàn)決定華法令阻凝劑藥物劑量的基因后，我們可能會(huì)很快解決病人藥物用量問(wèn)題,。
研究小組另一名顧問(wèn)李蘇秦博士告訴《今日》稱(chēng),，在去年為期2個(gè)多月的研究中，新加坡國(guó)立大學(xué)醫(yī)院的研究小組發(fā)現(xiàn)這種反復(fù)利用體內(nèi)維生素K的基因,，這種基因是華法令阻凝劑在抗凝結(jié)過(guò)程中攻擊的目標(biāo),。
此項(xiàng)研究的對(duì)象是275名中國(guó)、馬來(lái)西亞和印度病人,，他們父母和祖父母同樣來(lái)自相同種族。古博士認(rèn)為中國(guó)人和印度人的祖先絕大多數(shù)都是來(lái)自各自國(guó)家的南部地區(qū),。研究發(fā)現(xiàn)種族不同,，這種基因結(jié)構(gòu)也不相同。這就意味著印度人一天華法令阻凝劑的需求量為6mg,，而中國(guó)人需求量為3.5mg,，馬來(lái)西亞人的需求量介于印度人和中國(guó)人之間。
古博士補(bǔ)充到,，一個(gè)混血人可能具有“介于中間的”遺傳基因結(jié)構(gòu),，因此他可能就會(huì)需要一個(gè)介于中間的華法令阻凝劑藥物劑量。
此項(xiàng)研究成果刊登在1月份的《臨床藥理學(xué)和治療學(xué)》雜志上,。該雜志是一個(gè)國(guó)際知名的同行評(píng)審雜志,。鑒于此項(xiàng)研究具有重要的臨床應(yīng)用意義和短期投入應(yīng)用的前景，新加坡國(guó)立大學(xué)醫(yī)院將很快實(shí)施另一項(xiàng)計(jì)劃,，即在自愿者病人身上驗(yàn)證此項(xiàng)研究發(fā)現(xiàn),。
如果得到確認(rèn)，華法令阻凝劑可能就會(huì)成為全球首種能根據(jù)病人父母種族來(lái)決定處方藥劑量的藥物,。新加坡國(guó)立大學(xué)醫(yī)院同時(shí)正著手對(duì)另外10種藥物進(jìn)行研究,，這10藥物大部分為化療藥物,，以論證不同種族對(duì)這些藥物的反應(yīng)差異。古博士說(shuō),，“目前我們都是依據(jù)西方研究成果來(lái)開(kāi)處方”,。西方最近研究顯示白種人可能在藥物劑量的需求上要比非白種人更高。假如病人出現(xiàn)藥物副作用反應(yīng)我們應(yīng)當(dāng)如何應(yīng)對(duì)呢,？他表示,，盡管減少藥物劑量與最初使用藥物劑量一樣具有引發(fā)致命后果的可能性，但是我們所采取的首要一步還是要在后續(xù)治療中減少藥物劑量,。
古博士稱(chēng),，新加坡醫(yī)生在為病人開(kāi)化療藥物劑量時(shí)，醫(yī)生經(jīng)常不得不對(duì)約20%至30%的病人藥物劑量進(jìn)行修正,。
疫苗——癌癥病人的福音
一種針對(duì)一些最嚴(yán)重癌癥的新疫苗可以防止病人在首次外科手術(shù)或者藥物治療后出現(xiàn)復(fù)發(fā),。一個(gè)對(duì)來(lái)自英國(guó)和其它歐盟國(guó)家的700名腎癌病人進(jìn)行治療的計(jì)劃將在今年內(nèi)起動(dòng)。過(guò)去的經(jīng)驗(yàn)顯示這種治療是安全的,，它通過(guò)激發(fā)人體自身的免疫系統(tǒng)來(lái)攻擊腫瘤,。
直腸癌和乳腺癌同樣也被列入該疫苗臨床驗(yàn)證的計(jì)劃之中。明年一種名為Gardasil的能預(yù)防婦女子宮癌的新疫苗同時(shí)也有可能會(huì)面市,。倫敦南區(qū)ST喬治醫(yī)院的腫瘤教授格斯·達(dá)爾格里斯博士幫助開(kāi)發(fā)出了一種能有效預(yù)防前列腺癌的疫苗,，該疫苗目前正在英國(guó)全國(guó)范圍內(nèi)進(jìn)行大規(guī)模試驗(yàn)。
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.
