Department of Dermatology, Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
Department of Dermatology, Heilongjiang Provincial Hospital, Harbin 150001, China.
Biomed Res Int. 2020 Feb 11;2020:2867505. doi: 10.1155/2020/2867505. eCollection 2020.
Caspase recruitment domain family member 8 (CARD8) is an adaptor molecule that negatively regulates nuclear factor-B (NF-B) activation, interleukin (IL)-1 secretion, and apoptosis. These play important roles in the pathogenesis of psoriasis. Genetic variants of CARD8 have been associated with an increased risk of several inflammatory diseases and psoriasis in Europe. However, nothing is known about the association of the polymorphisms of CARD8 and psoriasis vulgaris (PsV) in the Han population of northeastern China. To investigate the potential association between them, we designed a case-control study to genotype four selected single nucleotide polymorphisms (SNPs) using the improved multiplex ligation reaction (iMLDR) method. Model-based single SNP frequentist-test and haplotype association studies were performed to assess the association between SNPs and PsV. The results showed that the intron SNP rs10403848 was significantly associated with PsV (additive model =0.0418, '=0.0411, and statistical power 0.1902; heterozygous model =0.0418, '=0.0164, and statistical power 0.9406). A potential risk locus of nonsynonymous SNP rs2043211 found in the European population did not show a significant association in our study. We found that the polymorphism rs10403848 in CARD8 is significantly associated with PsV risk in the Han population of northeastern China. CARD8 may be involved in PsV in this population, as in the European population, but a different genetic process should be considered for the heterogeneity of risk loci.
半胱氨酸天冬氨酸蛋白酶募集结构域家族成员 8（CARD8）是一种衔接分子，可负向调节核因子-B（NF-B）激活、白细胞介素（IL）-1 分泌和细胞凋亡。这些在银屑病的发病机制中起着重要作用。CARD8 的遗传变异与欧洲几种炎症性疾病和银屑病的风险增加有关。然而，在中国东北地区汉族人群中，CARD8 多态性与寻常型银屑病（PsV）之间的关联尚不清楚。为了研究它们之间的潜在关联，我们设计了一项病例对照研究，使用改良多重连接酶反应（iMLDR）方法对四个选定的单核苷酸多态性（SNP）进行基因分型。基于模型的单 SNP 频率测试和单倍型关联研究用于评估 SNP 与 PsV 之间的关联。结果表明，内含子 SNP rs10403848 与 PsV 显著相关（加性模型=0.0418，'=0.0411，统计功效 0.1902；杂合模型=0.0418，'=0.0164，统计功效 0.9406）。在欧洲人群中发现的非同义 SNP rs2043211 的潜在风险位点在我们的研究中没有显示出显著相关性。我们发现，CARD8 中的多态性 rs10403848 与中国东北地区汉族人群的 PsV 风险显著相关。CARD8 可能参与了该人群的 PsV，就像在欧洲人群中一样，但应该考虑不同的遗传过程来解释风险位点的异质性。
