A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1.
A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1.
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DOI：
10.1038/s41598-018-30665-6
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发表时间：
2018-08-15
影响因子：
4.6
通讯作者：
Rouleau GA
中科院分区：
文献类型：
--
作者：
Catoire H;Sarayloo F;Mourabit Amari K;Apuzzo S;Grant A;Rochefort D;Xiong L;Montplaisir J;Earley CJ;Turecki G;Dion PA;Rouleau GA
不宁腿综合征（RLS）是一种常见的睡眠障碍，其遗传贡献仍然很难解释。2007年，第一个大规模的全基因组关联研究（GWAS）确定了与RLS相关的三个基因组区域。MEIS 1、BTBD 9和MAP 2K 5/SKOR 1是位于这些基因座内的唯一已知基因，它们与RLS的关联随后在许多随访GWAS中得到证实。在这一发现之后，我们的研究小组报告了MEIS 1风险单倍型与其在mRNA和蛋白质水平上的表达降低相关。在这里，我们报告了与RLS密切相关的其他三个基因的风险变体的影响。虽然这些变体对携带它们的基因的mRNA水平没有影响，但我们发现同源框转录因子MEIS 1正调控转录辅阻遏物SKOR 1的表达。这种调节似乎是通过MEIS 1在位于SKOR 1启动子区的两个特异性位点的结合介导的，并通过基因启动子区中的RLS相关SNP进行修饰。我们的研究结果直接将MEIS 1和SKOR 1这两个与RLS显著相关的基因联系起来，并且在GWAS发现的与RLS相关的MAP 2K 5/SKOR 1基因间区域中，SKOR 1优先于MAP 2K 5。
Restless Legs syndrome (RLS) is a common sleep disorder for which the genetic contribution remains poorly explained. In 2007, the first large scale genome wide association study (GWAS) identified three genomic regions associated with RLS. MEIS1, BTBD9 and MAP2K5/SKOR1 are the only known genes located within these loci and their association with RLS was subsequently confirmed in a number of follow up GWAS. Following this finding, our group reported the MEIS1 risk haplotype to be associated with its decreased expression at the mRNA and protein levels. Here we report the effect of the risk variants of the three other genes strongly associated with RLS. While these variants had no effect on the mRNA levels of the genes harboring them, we find that the homeobox transcription factor MEIS1 positively regulates the expression of the transcription co-repressor SKOR1. This regulation appears mediated through the binding of MEIS1 at two specific sites located in the SKOR1 promoter region and is modified by an RLS associated SNP in the promoter region of the gene. Our findings directly link MEIS1 and SKOR1, two significantly associated genes with RLS and also prioritize SKOR1 over MAP2K5 in the RLS associated intergenic region of MAP2K5/SKOR1 found by GWAS.
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影响因子：
2.5
作者：
Longobardi, E.;Penkov, D.;Mateos, D.;De Florian, G.;Torres, M.;Blasi, Francesco
通讯作者：
Blasi, Francesco
DOI：
10.1093/bioinformatics/btp472
发表时间：
2009-10-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Nicol JW;Helt GA;Blanchard SG Jr;Raja A;Loraine AE
通讯作者：
Loraine AE
影响因子：
10.5
作者：
Ohayon MM;O'Hara R;Vitiello MV
通讯作者：
Vitiello MV
影响因子：
5.6
作者：
Moore, Hyatt;Winkelmann, Juliane;Mignot, Emmanuel
通讯作者：
Mignot, Emmanuel
影响因子：
11.2
作者：
Catoire, Helene;Dion, Patrick A.;Rouleau, Guy A.
通讯作者：
Rouleau, Guy A.