title: Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population.
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.
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
authors.forename: Aditi
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
authors.forename: Anirudhya
authors.initials: A
authors.lastname: Lahiri
authors.affiliation: Consultant Dermatologist, Uttarpara, Hooghly India 712258.
authors.forename: Swapan
authors.initials: S
authors.lastname: Senapati
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
authors.forename: Baidehi
authors.initials: B
authors.lastname: Basu
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
authors.forename: Indranil
authors.initials: I
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Dermatology, SSKM Hospital, Kolkata, India.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Behra
authors.affiliation: Department of Dermatology, School of Tropical medicine, Kolkata, India.
authors.forename: Somenath
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Dermatology, SSKM Hospital, Kolkata, India.
authors.forename: Gobinda
authors.initials: G
authors.lastname: Chatterjee
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, India 700108.
authors.forename: Raghunath
authors.initials: R
authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D012306:Risk
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; C000616471:LCE3A protein, human; C549748:LCE3B protein, human; C524768:LCE3C protein, human