Department of Neurology, Oslo University Hospital, Ullevål, Oslo 0407, Norway.
Int J Mol Sci. 2013 Feb 25;14(3):4476-97. doi: 10.3390/ijms14034476.
Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals, probably triggered by common environmental factors. Human leukocyte antigen (HLA) loci were early shown to confer the strongest genetic associations in MS. Now, more than 50 non-HLA MS susceptibility loci are identified, of which the majority are located in immune-regulatory genes. Single nucleotide polymorphisms (SNPs) in the C-type lectin-like domain family 16A (CLEC16A) gene were among the first non-HLA genetic variants that were confirmed to be associated with MS. Fine-mapping has indicated a primary association in MS and also other autoimmune diseases to intronic CLEC16A SNPs. Here, we review the identification of MS susceptibility variants in the CLEC16A gene region, functional studies of the CLEC16A molecule and the recent progress in understanding the implications thereof for MS development. This may serve as an example of the importance for further molecular investigation of the loci identified in genetic studies, with the aim to translate this knowledge into the clinic.
多发性硬化症（MS）是一种中枢神经系统的炎症性脱髓鞘疾病，发生于遗传易感性个体，可能由常见的环境因素触发。人类白细胞抗原（HLA）基因座很早就被证明与 MS 具有最强的遗传相关性。现在，已经确定了 50 多个非 HLA MS 易感性基因座，其中大多数位于免疫调节基因中。C 型凝集素样域家族 16A（CLEC16A）基因中的单核苷酸多态性（SNP）是最早被证实与 MS 相关的非 HLA 遗传变异之一。精细映射表明，MS 和其他自身免疫性疾病与内含子 CLEC16A SNP 之间存在主要关联。本文综述了 CLEC16A 基因区域中 MS 易感性变异的鉴定、CLEC16A 分子的功能研究以及对其在 MS 发病机制中意义的最新进展。这可以作为进一步研究遗传研究中确定的基因座的分子重要性的一个例子，目的是将这些知识转化为临床应用。
