为什么感冒会加重病情，帕金森症和免疫系统的关系以及非類固醇抗發炎藥物
帕金森氏症與免疫系統相關基因間的關聯性 (舊譯文)2012-08-11 06:22:11
Writing in Nature Genetics, researchers have found that a gene involved in the immune response is linked to the risk of developing Parkinson’s disease.
於《自然‧遺傳學》期刊中記述，研究人員們業已發現一種於免疫反應中被涉及的基因，與罹患帕金森氏症風險有所關聯。
The finding “is a small piece of a big puzzle,” said lead author Haydeh Payami, Ph.D., an investigator at the New York State Department of Health Wadsworth Center in Albany. However, it strengthens a theory that Parkinson’s disease may result partly from harmful immune reactions such as inflammation, infections or autoimmunity – when the immune system attacks the body’s own tissues.
首要撰文人，美國紐約州奧爾巴尼市紐約州立衛生署沃茲沃斯中心研究員Haydeh Payami博士宣稱：「此研究發現是大謎團中的一小片段。」不過，強化了帕金森氏症可能部分起因於，諸如發炎、感染或免疫系統攻擊自身組織之自體免疫等，有害免疫反應的理論。
Parkinson’s disease attacks neurons in the substantia nigra, a part of the brain that helps control movement. The most common symptoms of the disease are involuntary shaking, slow movement, stiffened muscle tone, and impaired balance.
帕金森氏症攻擊腦部協助控制行動之黑質部分中的神經元。該種疾病最常見的症狀是不自主的顫抖、行動緩慢、肌肉僵硬及平衡受損。
圖1. 黑質(substantia nigra) (圖援用自：http://whyfiles.org/127stem_cell/4.html)
There are rare purely genetic forms of Parkinson’s disease, but the disease usually is sporadic, meaning that the cause is unclear. In these sporadic cases, researchers suspect that the disease stems from an interplay of genetics and environmental factors. Among these, caffeine consumption and cigarette smoking are associated with a reduced risk of Parkinson’s disease, while there is some evidence that occupational exposure to pesticides increases the risk of the disease.
有罕見的純遺傳型帕金森氏症，不過該種疾病通常是偶發性的，意味著原因不明。於此些偶發性病例中，研究人員們懷疑，該種疾病起因於遺傳性及環境因素的相互作用。其中，消費咖啡因及吸煙與降低的帕金森氏症風險有關，但是有些證據顯示，職業性曝露於殺菌劑中，會增加該種疾病的風險。
More recently, investigators have linked a handful of genes to the risk of sporadic Parkinson’s. The two strongest linked genes, MAPT and SNCA, appear to be active primarily in neurons. MAPT encodes a structural protein inside neurons and SNCA encodes alpha-synuclein, a protein believed to regulate signaling both within and between neurons.
最近，研究人員們業已將少數基因與偶發性帕金森氏症的風險聯繫在一起。MAPT及SNCA這兩關聯性最強的基因，於神經元中，顯然本質上是活性的。MAPT為神經元內的結構蛋白質編譯密碼，而SNCA為α-突觸核蛋白編譯密碼。α-突觸核蛋白被認為是種調節神經元內及神經元間信號傳遞的蛋白質。
The new study identifies a variant of the HLA-DRA gene as a risk factor for Parkinson’s. HLA genes encode proteins that are displayed on the body’s cells to help the immune system distinguish self from non-self.
該項新研究確認HLA-DRA基因的變異體是帕金森氏症的風險因子。HLA基因為被顯露於體細胞上，以協助免疫系統識別自體與非自體的蛋白質編譯密碼。
The study involved nearly 4,000 participants, recruited through clinics affiliated with the NeuroGenetics Research Consortium (NGRC) in Oregon, Washington, New York and Georgia. About half of the participants had Parkinson’s and half did not. Their DNA samples were scanned for nearly 1 million single nucleotide polymorphisms (SNPs), which are tiny, usually harmless variants in the genetic code.
該項研究涉及了近4千名，透過俄勒岡、華盛頓、紐約及喬治亞州神經遺傳學研究聯合會附屬診所招募的參與者，其中約半數參與者罹患有帕金森氏症。他們的DNA樣本被掃描，達近1百萬個單核苷酸多態性，此些是遺傳密碼中通常無害的微小變異體。
In addition to finding an association between Parkinson’s disease and a variant in HLA-DRA, the study confirmed previously reported associations with SNCA, MAPT and a gene called GAK. The variant in HLA-DRA was most strongly associated with late-onset, sporadic cases and was seen more often in men, who are affected by sporadic Parkinson’s disease more often than women.
除了發現帕金森氏症與HLA-DRA中一個變異體間的關聯性之外，該項研究證實了，先前與SNCA、MAPT及被稱為GAK基因的關聯性報告。該於HLA-DRA中的變異體與晚發、偶發性病例的關聯性最為強烈，且較常在比女性更常遭偶發性帕金森氏症侵襲的男性中被發現。
The researchers also explored the combined effects of having risk variants in all four of the genes - HLA, SNCA, MAPT and GAK. Since everyone has two copies of each gene, the total possible number of risk variants is eight. The risk of Parkinson’s disease was doubled for individuals with four risk variants and five-fold higher for individuals with six or more risk variants.
此些研究人員也探索了，於HLA、SNCA、MAPT及GAK四種基因中具有危險變異體的綜合性效應。由於任何人的每一基因皆具有兩份複製物，因而可能的總危險變異體數是8個。就具有4個危險變異體的個體而言，帕金森氏症的風險是兩倍，而具有6個或更多個危險變異體的個體是五倍以上。
“Each of the genes associated with sporadic Parkinson’s disease has a very small impact on disease risk by itself, but additively, these genes can have a large impact,” said Dr. Payami.
Payami博士宣稱：「此些與偶發性帕金森氏症有關聯的每一基因，其本身對此疾病風險具有很小的衝擊性，不過加成上，此些基因能具有大的衝擊性。」
Considered with other bits of evidence, a connection between HLA-DRA and Parkinson’s should spur more research on immune system’s role in the disease, Dr. Payami said. Some studies have shown that there are signs of inflammation in the brains of patients, and that the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of the disease. Perhaps not coincidentally, a relative of HLA-DRA called HLA-DRB is the strongest known genetic risk factor for multiple sclerosis, a neurological disease caused by autoimmune reactions.
Payami博士表示，考量了其他若干證據，HLA-DRA與帕金森氏症間的關聯性將促使更多針對免疫系統於該疾病中的角色研究。有些研究業已證實，有諸多於病患腦部中發炎的徵兆及使用非類固醇抗發炎藥物，與較低的該種疾病風險有所關聯。或許並非巧合，因為一種被稱為HLA-DRB的HLA-DRA同類基因，是多發性硬化症已知最強的遺傳性風險因子，多發性硬化症是由自體免疫反應引發的一種神經系統疾病。
Dr. Payami and her colleagues found no interaction between HLA-DRA status and prior NSAID use. For example, there was no evidence that having a risk version of HLA-DRA canceled the beneficial effects of NSAID use, or vice versa. Determining the functional significance of HLA-DRA status in Parkinson’s disease will require further investigation, Dr. Payami said.
Payami博士及其同僚們並未發現，HLA-DRA狀態與上述使用非類固醇抗發炎藥物間的交互作用。譬如，並無HLA-DRA抵消了使用非類固醇抗發炎藥物之有利效益，或反之亦然的風險型證據。Payami博士表示，確認HLA-DRA狀態於帕金森氏症中的功能意義，將需進一步的研究。
Data from this study, as well as other Parkinson’s disease genome-wide association studies, are available from the dbGaP database, sponsored by NIH’s National Center for Biotechnology Information.
來自該項研究及其他帕金森氏症全基因體關聯性研究的數據，在由美國國家衛生研究院所屬國家生技資訊中心所發起的dbGaP database中可資取得。
The NGRC is led by Dr. Payami and is a project to gather information about genetic and environmental risk factors involved in Parkinson’s disease. The study was funded by the National Institute of Neurological Disorders and Stroke, and an award from The Michael J. Fox Foundation for Parkinson’s Research Edmond J. Safra Global Genetics Consortia initiative .
由Payami博士領導的神經遺傳學研究聯合會，宗旨在於收集有關帕金森氏症中被涉及之遺傳與環境風險因子的資訊。該項研究是由美國國家神經系統疾病暨中風研究所及其他研究機構所資助。
原文網址：http://www.ninds.nih.gov/news_and_events/news_articles/HLA_gene_parkinson_risk.htm
翻譯：許東榮
科普：重感冒可能增加帕金森氏症患病风险
www.PharmNet.com.cn 2012-07-23
加拿大一项最新研究显示，重感冒病人患上帕金森氏症的风险是健康人的两倍。研究报告已发表在《运动障碍》杂志的网络版上。
加拿大不列颠哥伦比亚大学的研究人员对比了403名帕金森氏症患者及405名健康人的相关数据后发现，重感冒病人患上帕金森氏症的风险是健康人的两倍，但儿时得过麻疹的人患上帕金森氏症的几率比普通人低35%。
研究人员表示，目前医学界对帕金森氏症的防治没有很好的对策，部分原因是人们还不了解帕金森氏症的发病机理。因此，这项研究有助于人们理解发病机理，并帮助开发出有效的预防办法。
所以建议在寒冬来临的时候，各位病友注意保暖，尽量减少感冒的次数，避免太强的免疫系统可能会加剧病情。
