不安腿综合征基因座在三个欧洲人群中的复制情况。
Replication of restless legs syndrome loci in three European populations.
作者信息
Kemlink D, Polo O, Frauscher B, Gschliesser V, Högl B, Poewe W, Vodicka P, Vavrova J, Sonka K, Nevsimalova S, Schormair B, Lichtner P, Silander K, Peltonen L, Gieger C, Wichmann H E, Zimprich A, Roeske D, Müller-Myhsok B, Meitinger T, Winkelmann J
机构信息
Helmholtz Zentrum Munich, National Research Center of Environment and Health, Institute of Human Genetics, Munich, Germany.
出版信息
J Med Genet. 2009 May;46(5):315-8. doi: 10.1136/jmg.2008.062992. Epub 2009 Mar 10.
BACKGROUND
Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q.
METHODS
Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms.
RESULTS
We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26 x 10(-5), odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11 x 10(-5), OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9.
CONCLUSION
Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.
背景
不宁腿综合征（RLS）与位于2号染色体、6号染色体和15号染色体上的MEIS1、BTBD9以及MAP2K5/LBXCOR1基因的三个内含子和基因间区域的常见变异有关。
方法
我们的研究在来自捷克共和国（290例患者和450名对照）、奥地利（269例患者和611名对照）以及芬兰（90例患者和169名对照）的649例RLS患者和1230名对照中对这些变异进行了研究。根据之前全基因组扫描的结果，在这三个基因组区域内选择了10个单核苷酸多态性（SNP）。使用Sequenom平台对样本进行基因分型。
结果
我们在合并样本集中重复验证了所有位点的关联性（MEIS1基因中的rs2300478，p = 1.26 x 10(-5)，优势比（OR） = 1.47；BTBD9基因中的rs3923809，p = 4.11 x 10(-5)，OR = 1.58；MAP2K5/LBXCOR1基因中的rs6494696，p = 0.04764，OR = 1.27）。仅分析家族性病例与所有对照，所有三个位点均显著相关。仅使用散发性病例，我们仅能确认与BTBD9的关联性。
结论
我们的研究表明，这三个位点的变异在欧洲血统患者中赋予了一致的疾病风险。在已知位点中，BTBD9对RLS的影响在不同人群中似乎最为一致，并且也最独立于家族聚集性。
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