Abstract
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.
Highlights
IntroductionMost of the studies among Indian population identified HLA-Cw6 as the most strongly associated loci[15,44,45]
The presence of HLA-Cw6 allele was determined for 705 psoriasis cases and 738 healthy controls using sequence specific PCR (SSP)
The risk imparted by HLA-Cw6 was more than two fold in type-I patients (OR = 6.61) compared to type-II patients (OR = 2.98) (Supplementary Table S2)
Summary
Most of the studies among Indian population identified HLA-Cw6 as the most strongly associated loci[15,44,45]. The association of LCE3 cluster with psoriasis has not been determined among Indian population. The functional implications of the combined effect of these risk variants were not reconnoitered. We have determined the involvement of all five LCE3 genes in the pathogenesis of psoriasis among Indian patients. We have analyzed the association of the LCE3C-3B deletion and three SNPs (rs1886734, rs4112788, rs7516108) within the LCE3 cluster among psoriasis patients in India. We determined the epistatic interaction of HLA-Cw6 and the LCE3 cluster, and appraised the functional implications of the combined effect of HLA-Cw6 and LCE3 risk variants
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