Institute of Human Genetics, Helmholtz Zentrum München e German Research Center for Environmental Health, Neuherberg, Germany.
J Med Genet. 2011 Jul;48(7):462-6. doi: 10.1136/jmg.2010.087858. Epub 2011 May 14.
Restless legs syndrome (RLS) is a sleep related movement disorder that occurs both in an idiopathic form and in symptomatic varieties. RLS is a frequent and distressing comorbidity in end stage renal disease (ESRD). For idiopathic RLS (iRLS), genetic risk factors have been identified, but their role in RLS in ESRD has not been investigated yet. Therefore, a case-control association study of these variants in ESRD patients was performed.
The study genotyped 10 iRLS associated variants at four loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, and PTPRD, in two independent case-control samples from Germany and Greece using multiplex PCR and MALDI-TOF (matrix assisted laser desorption/ionisation time-of-flight) mass spectrometry. Statistical analysis was performed as logistic regression with age and gender as covariates. For the combined analysis a Cochran-Mantel-Haenszel test was applied.
The study included 200 RLS-positive and 443 RLS-negative ESRD patients in the German sample, and 141 and 393 patients, respectively, in the Greek sample. In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (P(nom)≤0.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9 (P(nom)≤0.08, ORs 1.41 and 1.33). In the combined analysis including all samples, BTBD9 was associated after correction for multiple testing (P(corrected)=0.0013, OR 1.47).
This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated. The extent of the genetic predisposition could vary between different subgroups of RLS in ESRD.
不宁腿综合征（RLS）是一种与睡眠相关的运动障碍，既可以是特发性的，也可以是症状性的。RLS 是终末期肾病（ESRD）中常见且令人痛苦的合并症。对于特发性 RLS（iRLS），已经确定了遗传风险因素，但尚未研究其在 ESRD 中的作用。因此，对这些变体在 ESRD 患者中的病例对照关联研究进行了。
该研究使用多重 PCR 和 MALDI-TOF（基质辅助激光解吸/电离时间飞行）质谱法，在德国和希腊的两个独立病例对照样本中，对四个基因 MEIS1、BTBD9、MAP2K5/SKOR1 和 PTPRD 上的 10 个与 iRLS 相关的变体进行基因分型。统计分析作为逻辑回归进行，年龄和性别作为协变量。对于合并分析，应用 Cochran-Mantel-Haenszel 检验。
该研究纳入了德国样本中的 200 名 RLS 阳性和 443 名 RLS 阴性 ESRD 患者，以及希腊样本中的 141 名和 393 名患者。在德国样本中，MEIS1 和 BTBD9 中的变体与 ESRD 中的 RLS 相关（P(nom)≤0.004，ORs 1.52 和 1.55），而在希腊样本中，MAP2K5/SKOR1 和 BTBD9 有相关趋势（P(nom)≤0.08，ORs 1.41 和 1.33）。在包括所有样本的合并分析中，BTBD9 在经过多重测试校正后具有相关性（P(corrected)=0.0013，OR 1.47）。
这是首次证明 BTBD9 基因对 ESRD 患者 RLS 的遗传影响显著相关。遗传易感性的程度可能在 ESRD 中的不同 RLS 亚组之间有所不同。
