Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus
Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus
复制标题
DOI：
10.1046/j.1529-8817.2004.00118.x
复制
发表时间：
2004-11-01
影响因子：
1.9
通讯作者：
Novelli, G
中科院分区：
文献类型：
--
作者：
Giardina, E;Capon, F;Novelli, G
银屑病是一种慢性炎症性皮肤疾病，具有遗传和环境风险因素。非参数连锁分析已经在不同的染色体上定位了许多易感基因座。我们将其中一个位点PSORS4定位在人类染色体1q21上。使用连锁不平衡的方法，我们细化的关键区域，一个特定的基因组区间约100 Kb，其中只包含兜甲蛋白（LOR）基因。在这里，我们报告了该基因的遗传和功能研究，以验证其参与银屑病的发病机制。我们记录了LOR在银屑病患者皮肤中的低表达，这些患者选自与PSORS4基因座分离的家族。对一部分患者的整个基因进行重新测序，发现存在能够影响蛋白质结构的新型多态性，如分子建模研究所示。然而，在一个大的意大利核心家庭队列中没有发现遗传相关的证据。这排除了LOR基因作为PSORS4基因座的候选基因。
Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Nonparametric linkage analyses have mapped many susceptibility loci on different chromosomes. We mapped one of these loci, PSORS4, on human chromosome 1q21. Using the linkage disequilibrium approach, we refined the critical region to a specific genomic interval of about 100 Kb which contains only the loricrin (LOR) gene. Here we report a genetic and functional study of this gene to verify its involvement in psoriasis pathogenesis. We document low expression of LOR in psoriatic skin of patients selected from families in which the disease was segregrating with the PSORS4 locus. Re-sequencing of the entire gene in a subset of patients revealed the existence of novel polymorphisms able to influence the protein structure, as shown by molecular modelling studies. However, no evidence for genetic association was detected in a large cohort of Italian nuclear families. This rules out the LOR gene as a candidate for the PSORS4 locus.