Chandra Aditi, Lahiri Anirudhya, Senapati Swapan, Basu Baidehi, Ghosh Saurabh, Mukhopadhyay Indranil, Behra Akhilesh, Sarkar Somenath, Chatterjee Gobinda, Chatterjee Raghunath
Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
Consultant Dermatologist, Uttarpara, Hooghly India 712258.
Sci Rep. 2016 Apr 6;6:24059. doi: 10.1038/srep24059.
HLA-Cw6 is one of the most associated alleles in psoriasis. Recently, Late Cornified Envelop 3 (LCE3) genes were identified as a susceptibility factor for psoriasis. Some population showed epistatic interaction of LCE3 risk variants with HLA-Cw6, while some population failed to show any association. We determined the associations of a 32.2 kb deletion comprising LCE3C-3B genes and three SNPs (rs1886734, rs4112788; rs7516108) at the LCE3 gene cluster among the psoriasis patients in India. All three SNPs at the LCE3 gene cluster failed to show any association. In contrary, for patients with HLA-Cw6 allele, all three SNPs and the LCE3C-3B deletion showed significant associations. While, all five LCE3 genes were upregulated in psoriatic skin, only LCE3A showed significant overexpression with homozygous risk genotype compared to the non-risk genotype. LCE3B also showed significant overexpression in patients with HLA-Cw6 allele. Moreover, LCE3A showed significantly higher expression in patients bearing homozygous risk genotype in presence of HLA-Cw6 allele but not in those having non-risk genotype, demonstrating the combined effect of HLA-Cw6 allele and risk associated genotype near LCE3A gene. Integration of genetic and gene expression data thus allowed us to identify the actual disease variants at the LCE3 cluster among the psoriasis patients in India.
HLA - Cw6是银屑病中关联度最高的等位基因之一。最近，晚期角质化包膜3（LCE3）基因被确定为银屑病的一个易感因素。一些人群显示LCE3风险变异与HLA - Cw6存在上位性相互作用，而另一些人群则未显示出任何关联。我们确定了印度银屑病患者中包含LCE3C - 3B基因的32.2 kb缺失以及LCE3基因簇处的三个单核苷酸多态性（SNP，rs1886734、rs4112788；rs7516108）之间的关联。LCE3基因簇处的所有三个SNP均未显示出任何关联。相反，对于携带HLA - Cw6等位基因的患者，所有三个SNP以及LCE3C - 3B缺失均显示出显著关联。虽然在银屑病皮肤中所有五个LCE3基因均上调，但与非风险基因型相比，只有LCE3A在纯合风险基因型中显示出显著的过表达。LCE3B在携带HLA - Cw6等位基因的患者中也显示出显著过表达。此外，在存在HLA - Cw6等位基因的情况下，LCE3A在携带纯合风险基因型的患者中表达显著更高，而在具有非风险基因型的患者中则不然，这表明了HLA - Cw6等位基因和LCE3A基因附近风险相关基因型的联合作用。因此，整合遗传和基因表达数据使我们能够在印度银屑病患者中识别出LCE3基因簇处的实际致病变异。
