Background: Besides the HLA-Cw0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C an...Background: Besides the HLA-Cw0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the PSORS1C3 gene, the CDSN971T allele, CDSNTTC (619T-1236T-1243C) and CDSN5 (619T-1240G-1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris. Objectives: We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. Methods: We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA-Cw0602, α-helix coiled-coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence-based typing method. Results: The PSORS1C3582A allele, an SNP in the 3-untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early-onset psoriasis vulgaris (22.3%vs. 6.9%, odds ratio = 3.87, Pc =0.0000 072). The frequencies of CDSNTTC and CDSN971T were also significantly increased in patients with early-onset psoriasis vulgaris. Moreover, PSORS1C3582A, SNP n.9C,Cw0602 and HCRWWCC were in near complete linkage disequilibrium(LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9C-Cw0602-PSORS1C3582A-HCRWWCC was a major susceptibility haplotype in patients with early-onset psoriasis vulgaris (P < 10-7) and this risk haplotype also carried CDSNTTC and CDSN971T. Conclusions: The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.展开更多
文摘Background: Besides the HLA-Cw0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the PSORS1C3 gene, the CDSN971T allele, CDSNTTC (619T-1236T-1243C) and CDSN5 (619T-1240G-1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris. Objectives: We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. Methods: We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA-Cw0602, α-helix coiled-coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence-based typing method. Results: The PSORS1C3582A allele, an SNP in the 3-untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early-onset psoriasis vulgaris (22.3%vs. 6.9%, odds ratio = 3.87, Pc =0.0000 072). The frequencies of CDSNTTC and CDSN971T were also significantly increased in patients with early-onset psoriasis vulgaris. Moreover, PSORS1C3582A, SNP n.9C,Cw0602 and HCRWWCC were in near complete linkage disequilibrium(LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9C-Cw0602-PSORS1C3582A-HCRWWCC was a major susceptibility haplotype in patients with early-onset psoriasis vulgaris (P < 10-7) and this risk haplotype also carried CDSNTTC and CDSN971T. Conclusions: The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.
