Genética Molecular, Hospital Universitario Central Asturias-Servicio de Salud del Principado de Asturias, Oviedo, Spain.
BMC Med Genet. 2010 Mar 23;11:45. doi: 10.1186/1471-2350-11-45.
An association between a common deletion comprising the late cornified envelope LCE3B and LCE3C genes (LCE3C_LCE3B-del) and Psoriasis (Ps) has been reported. The expression of these LCE genes was induced after skin barrier disruption and was also strong in psoriatic lesions. The damage to the skin barrier could trigger an epidermal response that includes the expression of genes involved in the formation of skin barrier.
We determined the LCE3C_LCE3B-del genotype in 405 Ps patients and 400 healthy controls from a Northern Spain region (Asturias). These patients and controls were also genotyped for the rs4112788 single nucleotide polymorphism, in strong linkage disequilibrium with the LCE3C_B cluster. The LCE3B and LCE3C gene variant was determined in the patients through SSCA, DHPLC, and direct sequencing.
Allele and genotype frequencies did not differ between patients and controls for the rs4112788 and LCE3C_LCE3B-del polymorphisms. However, del/del homozygotes were significantly higher among patients with chronic plaque type Ps who did not develop arthritis (p = 0.03; OR = 1.4; 95%CI = 1.03-1.92). The analysis of the coding sequence of LCE3B and LCE3C in the patients who had at least one copy of this showed that only one patient has a no previously reported LCE3B variant (R68C).
Our work suggested that homozygosity for a common LCE3C_LCE3B deletion contributes to the risk of developing chronic plaque type Ps without psoriatic arthritis. Our work confirmed previous reports that described an association of this marker with only skin manifestations, and supported the concept of different genetic risk factors contributing to skin and joint disease.
已经报道了晚期角蛋白包膜 LCE3B 和 LCE3C 基因（LCE3C_LCE3B-del）的常见缺失与银屑病（Ps）之间的关联。这些 LCE 基因的表达在皮肤屏障破坏后被诱导，并且在银屑病病变中也很强。皮肤屏障的损伤可能会引发表皮反应，包括参与皮肤屏障形成的基因的表达。
我们在来自西班牙北部阿斯图里亚斯地区的 405 名 Ps 患者和 400 名健康对照者中确定了 LCE3C_LCE3B-del 基因型。这些患者和对照者还对 rs4112788 单核苷酸多态性进行了基因分型，该多态性与 LCE3C_B 簇紧密连锁。通过 SSCA、DHPLC 和直接测序确定患者中 LCE3B 和 LCE3C 基因变异。
rs4112788 和 LCE3C_LCE3B-del 多态性的等位基因和基因型频率在患者和对照者之间没有差异。然而，在未发生关节炎的慢性斑块型 Ps 患者中，del/del 纯合子明显更高（p=0.03；OR=1.4；95%CI=1.03-1.92）。对至少携带一份这种缺失的患者的 LCE3B 和 LCE3C 编码序列进行分析，结果表明只有一位患者存在先前未报道的 LCE3B 变异（R68C）。
我们的工作表明，常见的 LCE3C_LCE3B 缺失纯合子有助于发生无银屑病关节炎的慢性斑块型 Ps 的风险。我们的工作证实了先前的报告，即该标记物仅与皮肤表现相关联，并支持了不同的遗传风险因素导致皮肤和关节疾病的概念。
