腿多动综合症基因发现

Gene Linked to Restless Leg Syndrome Found
07.18.07, 12:00 AM ET

WEDNESDAY, July 18 (HealthDay News) -- Icelandic researchers have discovered a gene that's linked to restless legs syndrome (RLS).
The research, which is in the July 19 issue of the New England Journal of Medicine, found a gene variant that increases the odds of having RLS with periodic limb movements during sleep by 50 percent. The researchers also found that those with the gene variant were more likely to have low iron levels.

\"There is a strong familial and genetic basis to restless legs syndrome,\" said the author of an accompanying editorial, Dr. John Winkelman, medical director of the Sleep Health Center at Brigham and Women's Hospital in Boston.

Winkelman's editorial also pointed out that two other soon-to-be-published studies confirmed the link to this gene variant and RLS in a different population, and found two other genetic variants linked to RLS.

\"Finding these genes may allow us to get more detail in the RLS story and eventually may allow us to predict who will respond to medications, who will have complications and which family members are likely to develop RLS. But it's early on; we need to see which of the next steps pan out, but this opens up many new avenues for research,\" Winkelman said.

Restless legs syndrome is a common neurological disorder, affecting as many as 3 percent of American adults, according to Winkelman. Those with RLS experience a compelling need to move their legs.

\"It's quite a creepy, uncomfortable feeling. It's kind of a jittery feeling that they have to move their legs,\" explained Susan Zafarlotfi, clinical director of the Institute for Sleep-Wake Disorders and the Breath and Lung Institute at Hackensack University Medical Center in New Jersey.

About four out of five people with RLS also experience periodic limb movements during sleep, according to Winkelman. Periodic limb movements -- jerking or twitching of the legs or feet -- occur in a fairly set pattern, with a still period in between. \"It almost looks as if they're guided by a metronome,\" said Winkelman. With each movement, blood pressure rises, and the person may be briefly aroused from sleep, though they're often not aware of this. Winkelman said many people with RLS have poor quality sleep and report daytime fatigue.

Many people with RLS also have family members with the disorder, suggesting a genetic component to the disease.

To locate any genetic variants that could be responsible for RLS, the researchers recruited 451 people who had symptoms of RLS, as well as 514 of their first-degree relatives.

The study volunteers filled out RLS questionnaires, had their periodic limb movements measured during sleep and gave blood samples.

The researchers found one genetic variant was strongly associated with RLS with periodic limb movements. To validate these findings, the researchers then compared a second sample of 123 Icelandic study participants to 1,233 controls.

Overall, people with that particular genetic variant were 50 percent more likely to have RLS with periodic limb movements. Because the association was stronger in people with RLS and periodic limb movements than in those with just RLS, the researchers and Winkelman believe this genetic variant is likely one associated with periodic limb movements.

The researchers also found that iron levels were significantly decreased -- by as much as 26 percent -- in those with the genetic variant.

\"Iron is important in the brain in the regulation of dopamine function. Dopamine is a neurotransmitter that's at least partially responsible for regulating sensation and movement,\" said Winkelman, who added that medications that increase dopamine activity in the brain, such as ropinirole (Requip) or pramipexole (Mirapex), are effective in treating RLS.

Both Winkelman and Zafarlotfi said that there's an increasing awareness in the medical community of RLS as a disorder, and that people should definitely bring it up with their physician if they're having symptoms.

\"Even if you were rebuffed originally when describing your symptoms, try again,\" advised Winkelman. He said an appropriate assessment includes checking blood levels of iron and reviewing what medications you're taking.

Zafarlotfi pointed out that some common medications, such as antidepressants, may increase RLS symptoms.


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腿多动综合症基因发现

07.18.07, 12:00 AM ET

07月18号，星期三（健康日报新闻）—冰岛研究人员已经发现一个腿多动症基因（RLS）.该研究发现，一个基因突变使在睡觉时患RLS（伴随周期性肢体运动）的几率增加50%，研究人员还发现，那些有该基因突变的人群铁离子含量普遍偏低。该研究结果发表在新英格兰医学杂志七月19日刊。
一篇相关社论的作者Dr. John Winkelman（波士顿布理格姆妇女医院睡眠健康中心医学主任）博士指出“腿多动综合症具有较强的家族遗传背景” Winkelman社论同时指出，另外两篇即将发表的研究论文证实了在不同人群中这个基因突变与RLS有关联，以及发现另外两个与RLS相关的遗传突变。
Winkelman解释说，“这些基因的发现可以使我们更详细地了解RLS发病过程，最终帮助我们预测谁会对药物治疗有反映，谁会有并发症，以及那些家族成员更容易患RLS。但是，目前为时还早；我们需要看接下来哪步会成功，然而也带来许多新的研究途径。”
按照Winkelman的报告，腿多动综合症是一种常见的神经紊乱疾病，影响多达3%的美国成年人，患有RLS的人需要强制性切除大腿。
新泽西州哈肯萨克河大学医学中心呼吸与肺病研究所和睡眠紊乱研究所的临床主任Susan Zafarlotfi解释说，他们不得不切除大腿给人产生一种紧张不安的情绪，令人毛骨悚然，感觉很不舒服。
Winkelman指出，“大约五分之四的RLS患者在睡觉时会有周期性的肢体运动。周期性的肢体运动——腿或脚以一种设置好的程序摇动或抽搐，运动之间有一个平静阶段，似乎他们受到节拍器的指导。伴随每一个动作，血压会升高，患者都会暂时从睡眠中被唤醒，尽管他们经常意识不到这点。 很多RLS患者睡眠质量都很差，反应白天感觉疲劳。另外，许多RLS患者的家庭成员也有类似的精神紊乱，暗示该疾病具有遗传因素。”
为了定位导致RLS的所有基因变异，研究人员招募了有RLS症状的451名患者和他们的514名直属亲人。研究自愿者填写了RLS调查问卷，测量了他们睡眠过程中的周期性肢体的运动，并提供了血液样本。
研究人员发现一种基因变体与RLS的周期性肢体运动十分相关。为了证实这些研究结果，他们后来将第二份来自冰岛的123名志愿者样品与1233份对照样品做了比较。
总体看来，拥有那一特异性基因变体的人群患伴随周期性肢体运动的RLS几率高出50%。因为同时患有RLS和周期性肢体运动的人们比仅患有RLS的人们与基因变体相关性更强，研究人员和Winkelman认为这一基因变体很可能与周期性肢体运动有关。研究人员也发现拥有基因变体的患者体内的铁含量明显下降26%。
Winkelman指出：“铁离子对调节大脑中多巴胺功能很重要。多巴胺是一种神经递质，至少部分负责调节敏感度和运动，能增加多巴胺在大脑中活性的治疗药物对于治疗RLS很有效，如普拉克索或罗匹尼克。”
Winkelman和Zafarlotfi两人都谈到在医学界RLS越来越被认为是一种精神紊乱，如果他们有症状，他们应该明确告知他们的内科医生。那些有RLS症状的人应该明确告诉他们的内科医生。
Winkelman建议说：“即使当你刚开始描述你的症状时遭到回绝，可以不断尝试。”他认为测量血液中的铁离子水平和检查你正在服的药物是一个不错的评估方法。
最后，Zafarlotfi指出一些常用的药物治疗，包括抗抑郁药，可能加重RLS症状。