LRCH1 polymorphisms linked to delayed encephalopathy after acute carbon monoxide poisoning identified by GWAS analysis followed by Sequenom MassARRAY® validation
LRCH1 polymorphisms linked to delayed encephalopathy after acute carbon monoxide poisoning identified by GWAS analysis followed by Sequenom MassARRAY® validation
复制标题
通过 GWAS 分析和 Sequenom MassARRAY(R) 验证，鉴定出 LRCH1 多态性与急性一氧化碳中毒后迟发性脑病相关。
DOI：
10.1186/s12881-019-0931-7
复制
发表时间：
2019-12-16
影响因子：
--
通讯作者：
Gu, Renjun
中科院分区：
文献类型：
--
作者：
Gu, Jiapeng;Zeng, Jiao;Gu, Renjun
背景资料：本研究旨在探讨富含亮氨酸重复序列和含钙调蛋白同源结构域1（LRCH 1）基因多态性与急性一氧化碳中毒后迟发性脑病（DEACMP）遗传易感性的关系，为DEACMP的发病机制、诊断和预后研究提供理论依据。通过全基因组关联分析，选择LRCH 1的4个单核苷酸多态性rs 1539177（G/A）、rs 17068697（G/A）、rs 9534475（A/C）和rs 2236592（T/C）作为候选基因，对661例患者进行基因分型（DEACMP组：235例; ACMP组：426例）使用Sequenom Massarray（R）。在不同的遗传模型下对4个SNP位点与LRCH 1进行关联分析。LRCH 1多态性（rs 1539177，rs 17068697，rs 9534475）在加性和显性遗传模型下与DEACMP风险增加显著相关，LRCH 1基因rs 2236592多态性仅在显性模式下对DEACMP易感，在隐性模式下对DEACMP易感TT/TC + CC，OR = 1.616，95% CI：1.092-2.390，P = 0.015784。此外，LRCH 1基因rs 9534475多态性A等位基因可能增加DEACMP的发病风险（OR = 1.273，95%CI：1.013-1.601，P = 0.038445）。LRCH 1基因rs 9534475多态性A等位基因可能是DEACMP的危险因素。
Background: We explored the association of leucine-rich repeats and calponin homology domain containing 1 (LRCH1) gene polymorphisms with genetic susceptibility to delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), which might provide a theoretical basis for the pathogenesis, diagnosis, and prognosis research of DEACMP.Methods: Four single nucleotide polymorphisms, rs1539177 (G/A), rs17068697 (G/A), rs9534475 (A/C), and rs2236592 (T/C), of LRCH1, selected as candidate genes through genome-wide association analysis, were genotyped in 661 patients (DEACMP group: 235 cases; ACMP group: 426 cases) using Sequenom Massarray (R). The association analysis of four SNPs and LRCH1 was performed under different genetic models.Results: LRCH1 polymorphisms (rs1539177, rs17068697, rs9534475) under additive and dominant genetic models were significantly associated with an increased risk of DEACMP, but no significant association under allele and recessive models was found. The LRCH1 rs2236592 polymorphism was susceptible to DEACMP only under the dominant model (TT/TC + CC, OR = 1.616, 95% CI: 1.092-2.390, P = 0.015784). In addition, the A allele gene of rs9534475 polymorphism in LRCH1 might increase the risk for DEACMP (OR = 1.273, 95% CI: 1.013-1.601, P = 0.038445).Conclusions: We found a significant association between the four LRCH1 polymorphisms and DEACMP. The allelic A of rs9534475 polymorphism in LRCH1 might be a risk factor for DEACMP.