Correlation Of Rs151823 Polymorphism Within ERAP1 Gene With Some Clinical Features Of Psoriasis Vulgaris In Chinese Han Population

Background Psoriasis (OMIM*177900) is a chronic and relapsing inflammatory skin disease, the most common characteristics of which are erythematous, scaly plaques. It is an in?ammatory dermato-sis affecting 0.123% of Chinese Han population with a complex immunologic basis, which includes keratinocyte hyperproliferation, aberrant differentiation of the epidermis. Both strong genetic component and multiple environment factor playing an important role in presentation of disease. Psoriasis vulgaris (PV) is the most frequent clinical type, which take percent more than 90% of all psoriasis patients. We found a distinguished correlation of rs151823 polymorphism in ERAP1 gene region with psoriasis vulgaris in Chinese Han Population by genome-wide association study (GWAS). ERAP1 that lies on chromosome 5q15 is a novel psoriasis susceptibility loci.Objective To study the association between SNP rs151823 within ERAP1 locus and some phenotypes of psoriasis vulgaris in Chinese Han population basing on stratifying analysis of the age of onset, family history and clinical types, and to lay solid genetic foundation for the pathogenesis of psoriasis.Methods We analyzed the distributions of genotype and allele of rs151823 (polymorphic site within ERAP1 locus) in 7,717 cases and 11,831 normal controls, which derived from the previous psoriasis GWAS carried out by our group. Genotype data of the SNP were obtained from our previous genome wide assosiation study. The appropriate application of social science statistical software package SPSS 15.0 was used for statistical analysis of data. Chi square test was used for comparing genotype or allelic frequencies distribution among the groups. P-values below 0.05 were considered to be statistically significant.Results 1. The genotype frequencies of rs151823 (polymorphic site within ERAP1 gene) were of statistical significance between the cases and the controls (χ²=34.25, df=2, P=3.65×10^-8), there was a similar trend for the allelic frequencies (χ²=31.60, df=1, P=1.89×10^-8, OR 1.12, 95%CI 1.08-1.17). 2. The genotype and allelic frequencies of rs151823 polymorphism were statistical significance between the early-onset (Type I,≤40 years) cases and controls (genotype:χ²=40.52, df=2, P=1.59×10^-9; allele:χ²=37.69, df=1, P=8.28×10^-10, OR 1.14, 95%CI 1.09-1.19). But the genotype and allelic frequencies of rs151823 polymorphism were not statistical significance between the late-onset (Type II, >40 years) cases and controls (genotype:χ²=0.17, df=2, P=0.92; allele:χ²=0.01, df=1, P=0.91, OR 1.01, 95%CI 0.92-1.10). Meanwhile, there were statistical significance between the early-onset (Type I) cases and the late-onset (Type II) cases (genotype:χ²=7.37, df=2, P=0.025, PAA=0.04, PCA=0.86, PCC=0.018; allele:χ²=6.96, df=1, P=0.008, OR 1.14, 95%CI 1.03-1.25). 3. The genotype and allelic frequencies of rs151823 polymorphism were statistical significance between the pediatric age of onset cases and controls(genotype:χ²=21.81, df=2, P=1.84×10^-5; allele:χ²=18.86, df=1, P=1.41×10^-5, OR 1.16, 95%CI 1.09-1.25). There were also statistical significance between the adult age of onset cases and controls (genotype:χ²=22.43, df=2, P=1.35×10^-5; allele:χ²=21.38, df=1, P=3.76×10^-6, OR 1.11, 95%CI 1.06-1.16). However, there weren't statistical significance between the pediatric age of onset cases and adult age of onset cases (genotype:χ²=2.93,df=2, P=0.23, P_AA=0.68, P_CA=0.30, P_CC=0.09; allele:χ²=1.58, df=1, P=0.21, OR 1.05, 95%CI 0.97-1.13). 4. The genotype and allelic frequencies of rs151823 polymorphism within ERAP1 gene region were statistical significance between the familial cases and controls (genotype:χ²=22.30,df=2, P=1.43×10^-5; allele:χ²=21.53, df=1, P=3.48×10^-6, OR 1.18, 95%CI 1.10-1.26). There were also statistical significance between the sporadic cases and controls (genotype:χ²=22.14, df=2, P=1.56×10^-5; allele:χ²=20.06, df=1, P=7.50×10^-6, OR 1.11, 95%CI 1.06-1.16). However, there weren't statistical significance between the familial cases and sporadic cases (genotype:χ²=2.81, df=2, P=0.25, P_AA=0.16, P_CA=0.86, P_CC=0.19; allele:χ²=2.70, df=1, P=0.10, OR 1.06, 95%CI 0.99-1.15). 5. The genotype and allelic frequencies of rs151823 polymorphism within ERAP1 gene region were statistical significance between the acute guttate cases and controls (genotype:χ²=10.22, df=2, P=0.006; allele:χ²=7.09,df=1, P=0.008, OR 1.10, 95%CI 1.02-1.17). There were also statistical significance between the chronic plaque cases and controls (genotype:χ²=31.40, df=2, P=1.52×10^-7; allele:χ²=30.28, df=1, P=3.74×10^-8, OR 1.13, 95%CI 1.08-1.19). However, there weren't statistical significance between the chronic plaque and acute guttate cases (genotype:χ²=2.30, df=2, P=0.32, P_AA=0.14, P_CA=0.22, P_CC=0.93; allele:χ²=0.93, df=1, P=0.34, OR 1.04, 95%CI 0.96-1.11).Conclusion 1. The results indicate that the rs151823 polymorphism within ERAP1 gene is associated with psoriasis susceptibility in Chinese Han population, especially for the Type I (early onset) psoriasis. 2. The genotype and allelic frequencies of rs151823 polymorphism were statistical significance between the early-onset cases and the late-onset cases. ERAP1 gene was preferentially associated with Type I (early onset) psoriasis in Chinese Han population. 3. The rs151823 polymorphism within ERAP1 gene isn't associated with family history of psoriasis vulgaris. 4. The rs151823 polymorphism within ERAP1 gene isn't associated with clinical type of psoriasis vulgaris. 5. Our findings indicate that the polymorphism of ERAP1 gene (rs151823) have determinate effection on the age of onset, especially the early-onset (Type I) psoriasis, but have no effection on the family history and clinical types, which may be associated with complex psoriasis genetic backgroud and different pathogenesis.