Detecting Genetic Associations between ATG5 and Lupus Nephritis by trans-eQTL.
Detecting Genetic Associations between ATG5 and Lupus Nephritis by trans-eQTL.
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DOI：
10.1155/2015/153132
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发表时间：
2015
影响因子：
4.1
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zhang YM;Cheng FJ;Zhou XJ;Qi YY;Hou P;Zhao MH;Zhang H
目标。许多基因座被鉴定为干扰反式基因的表达。由于ATG5在系统性红斑狼疮(SLE)中的表达升高，本研究旨在分析与中国狼疮性肾炎(LN)人群中ATG5表达相关的全基因组遗传调控机制。方法：研究方法。检索在线表达数量性状基因座数据库，寻找ATG5的反式表达单核苷酸多态。用定制的基因分型芯片对280例患者和199例对照的反式eSNPs进行基因分型。对于阳性结果，进行了临床信息和生物信息分析。结果。有4个反式eSNP与LN的易感性相关(P<；0.05)，包括ANKRD50 rs17008504、AGA rs2271100、PAK7 rs6056923和TET2 rs1391441，而另外7个反式eSNP与LN的易感性存在边缘显著关联(0.05<；P<；0.1)。验证了SLE患者和对照组中反式eSNPs和ATG5的表达与ATG5不同表达水平的相关性，并解释了它们的调节作用。然而，不同的反式eSNPs基因类型与患者的严重程度或预后之间没有明显的关联。结论。利用新的系统遗传学方法，我们确定了10个可能与LN易感性相关的基因座，这可能是对未来基于途径的遗传学研究的补充。
Objectives. Numerous loci were identified to perturb gene expression in trans. As elevated ATG5 expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated with ATG5 expression in a Chinese population with lupus nephritis (LN). Methods. The online expression quantitative trait loci database was searched for trans-expression single nucleotide polymorphisms (trans-eSNPs) of ATG5. Tagging trans-eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed. Results. Four trans-eSNPs were observed to be associated with susceptibility to LN (P < 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven other trans-eSNPs showed marginal significant associations (0.05 < P < 0.1). Correlations between the trans-eSNPs and ATG5 expression and different expression levels of ATG5 in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes of trans-eSNPs and severity or outcome of the patients. Conclusion. Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.