Genetic Variation in the REL Gene Increases Risk of Behcet's Disease in a Chinese Han Population but That of PRKCQ Does Not.
Genetic Variation in the REL Gene Increases Risk of Behcet's Disease in a Chinese Han Population but That of PRKCQ Does Not.
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DOI：
10.1371/journal.pone.0147350
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hou S
中科院分区：
文献类型：
--
作者：
Chen F;Xu L;Zhao T;Xiao X;Pan Y;Hou S
全基因组关联研究（GWAS）和候选基因研究已经确定了REL和PRKCQ基因作为各种自身免疫性疾病的风险位点。本研究的目的是探讨REL和PRKCQ基因与中国汉族人群白塞病（BD）的相关性。对REL基因rs 13031237、rs702873和rs 842647三个单核苷酸多态性（SNPs）和三个SNPs进行病例对照研究使用聚合酶链反应-限制性片段长度多态性检测PRKCQ基因的rs 4750316、rs 11258747和rs 947474在总共623名BD患者和1，074名健康对照中进行了PCR-RFLP。评估了多个变量，包括年龄、性别分布和眼外结果。在本研究中，患者中rs 842647 GG基因型和rs 842647 G等位基因的频率显著高于对照组，而患者中rs 842647 AG基因型的频率显著低于对照组[GG基因型：性别校正的Bonferroni校正P值（Pca）= 0.0074，比值比（OR）= 1.63; G等位基因：AG基因型：Pca = 0.024，OR = 0.63]。在BD患者和对照组之间未观察到rs702873、rs 13031237、rs 4750316、rs 11258747和rs 947474频率的统计学显著差异。分层分析显示REL基因rs 842647多态性与BD患者皮肤损害相关。其他5个SNP位点与BD患者的其他眼外表现（包括生殖器溃疡、关节炎和皮肤病理学检查结果阳性）无显著相关性，提示REL rs 842647多态性可能是BD发病和皮肤病变的易感因素，提示c-Rel可能通过NF-κB通路参与BD的发病和皮肤病变。
Genome-wide association studies (GWAS) and candidate gene studies have identified the REL and PRKCQ genes as risk loci for various autoimmune diseases. The purpose of the present study was to investigate the association of the REL and PRKCQ genes with Behcet’s disease (BD) in a Chinese Han population. A case-control study was conducted on three single nucleotide polymorphisms (SNPs), rs13031237, rs702873, and rs842647 of the REL gene and three SNPs (rs4750316, rs11258747, and rs947474) of the PRKCQ gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a total of 623 BD patients and 1,074 healthy controls. Multiple variables were assessed, including age, sex distribution, and extra-ocular findings. In the present study, the frequencies of rs842647 GG genotypes and rs842647 G alleles were significantly higher in patients than in controls and those of the rs842647 AG genotypes were lower in patients than in controls [GG genotype: Bonferroni corrected P-value for gender adjustment (Pca) = 0.0074, odds ratio (OR) = 1.63; G allele: Pca = 0.0072, OR = 1.57; AG genotype: Pca = 0.024, OR = 0.63, respectively]. No statistically significant differences in the frequencies of rs702873, rs13031237, rs4750316, rs11258747, and rs947474 between BD patients and controls were observed. Stratification analysis indicated that the REL rs842647 polymorphism was associated with BD patients with skin lesions. No significant association of the other five SNPs between BD patients with other extra-ocular findings, including genital ulcer, arthritis, and positive pathergy test results was found. The REL rs842647 polymorphism may be a susceptibility factor for BD pathogenesis and skin lesions, which indicate that c-Rel may be involved in the pathogenesis and skin lesions of BD through the NF-κB pathway.