Luo Weiguang, Zhou Bin, Luo Qizhi, Fang Huilong, Zuo Xiaoxia, Zou Yizhou
Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
PLoS One. 2017 Oct 13;12(10):e0186409. doi: 10.1371/journal.pone.0186409. eCollection 2017.
Both systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) diseases are related to the genetic and environmental factors, causing damage to the skin. The mutations of keratin 1 gene (KRT1) were reported to associate with skin diseases. The single-nucleotide polymorphism (SNP, rs14024) and the indel polymorphism (cds-indel, rs267607656), consisting mostly of the common haplotypes and could be used for genotyping of KRT1. We used the PCR with sequence specific primers (PCR-SSP) to determine the genotype of KRT1 in 164 SLE, 99 SSc patients, and 418 healthy controls. The results showed that the mutant with G at SNP rs14024 was associated with the high risk to SLE (p = 6.48×10-5) and SSc (p = 8.75×10-5), while the deletion allele at rs267607656 was associated with the low risk to SSc (p = 4.89×10-4) comparing to the normal controls. Haplogenotype, Del-/MU+ was associated with high susceptibility to SLE (OR = 1.87, p = 0.001) and SSc (OR = 2.29, p = 2.34×10-4). In contrast, the Haplogenotype Del+/MU- was associated with resistance to SLE (OR = 0.35, p = 6.24×10-5) and SSc (OR = 0.34, p = 0.001). This study demonstrates that the variations in KRT1 and the specific polymorphism of KRT1 in this Chinese Han population are associated with autoimmune diseases SLE and SSc. Typing KRT1 might be helpful to identify SLE and SSc patients.
系统性红斑狼疮（SLE）和系统性硬化症（SSc）均与遗传和环境因素相关，可导致皮肤损伤。据报道，角蛋白1基因（KRT1）突变与皮肤病有关。单核苷酸多态性（SNP，rs14024）和插入缺失多态性（编码区插入缺失，rs267607656），主要由常见单倍型组成，可用于KRT1基因分型。我们采用序列特异性引物聚合酶链反应（PCR-SSP）测定了164例SLE患者、99例SSc患者和418例健康对照者的KRT1基因型。结果显示，SNP rs14024位点携带G的突变体与SLE（p = 6.48×10-5）和SSc（p = 8.75×10-5）的高风险相关，而与正常对照相比，rs267607656位点的缺失等位基因与SSc的低风险相关（p = 4.89×10-4）。单倍型Del-/MU+与SLE（OR = 1.87，p = 0.001）和SSc（OR = 2.29，p = 2.34×10-4）的高易感性相关。相反，单倍型Del+/MU-与SLE（OR = 0.35，p = 6.24×10-5）和SSc（OR = 0.34，p = 0.001）的抗性相关。本研究表明，中国汉族人群中KRT1的变异及KRT1的特定多态性与自身免疫性疾病SLE和SSc相关。对KRT1进行基因分型可能有助于识别SLE和SSc患者。
