Genetic Model Analysis Of AIM2 Single Nucleotide Polymorphism In Han Chinese Patients With Psoriasis

Background Psoriasis is a common, T cell‐mediated, inflammatory skin disorder,affects about 1%–3% of the population worldwide. Its clinical features are white scales, shiny film and spotting. The pathogenesis of psoriasis is not fully understood,but family history and environmental risk factors are recognized. Recently, our team presented a large‐scale whole‐exome array analysis for psoriasis and discovered that, AIM2 was one of the new genes/loci associated with psoriasis. Genotype phenotype correlation and genetic model analysis will help further reveal the etiology and pathogenesis of psoriasis.Objective According to the stratifying analysis of psoriasis, ie: skin lesion, the severity of disease and family history, we did the association study: the relation of AIM2 rs2276405 polymorphism between psoriasis clinical phenotypes and genetic model. It will help explain AIM2 rs2276405 polymorphism in the role of psoriasis etiology and pathogenesis.Methods 16876 unrelated cases and 22920 unrelated controls were recruited in this study. The clinical information was gathered by the same questionnaire. Genotype data of the AIM2 SNP was obtained from the large‐scale whole exome array analysis.We analyze the association between SNP and phenotypes and genetic model of psoriasis using Chi square test with SPSS20.0 and PLINK 1.07. Finally, we calculated the P‐value, odds ratio(OR) and 95% confidence interval(95%CI). And P < 0.05 was considered statistically significant.Results 1.AIM2 rs2276405 polymorphism was significantly correlated with psoriasis in Chinese Han population(PAIM2=3.22×10‐08, OR=0.83).2. The frequencies distribution of genotypes and alleles for AIM2 rs2276405 were no significant in skin lesion group, severity and family history group and control.3. To study potential associations between the gene and skin lesion, PASI score and family history, a stratified analysis of the genetic model was implemented for AIM2rs2276405 polymorphism, the dominant model provided the best fit for AIM2rs2276405. First, a statistically increased frequency of the dominant model was found in skin lesion, guttate( P=2.87×10‐7, OR=0.79, 95%CI=0.72‐0.86),plaque( P=8.39×10‐4, OR=0.88, 95%CI=0.81‐0.95),respectively. Second, combined with controls, a significantly increased frequency of the dominant model was found in the patients with mild and moderate(P=1.10×10‐7,OR=0.83,95%CI=0.78‐0.89), whereas the dominant model frequency in patients with severe was not statistically different from that in controls(P=3.62×10‐1,OR=0.91,95%CI=0.74‐1.12). Third, the frequency of the dominant model was found statistically higher in the sporadic psoriasis than that in the controls(P=6.85×10‐8,OR=0.82,95%CI=0.77‐0.88). While the frequency of the dominant model in the familial psoriasis was similar to that of the controls(P=1.01×10‐1,OR=0.90,95%CI=0.79‐1.02).Conclusions AIM2 rs2276405 is significantly associated with susceptibility of psoriasis in Han Chinese population. In all subtypes of psoriasis, the dominant model provided the best fit for AIM2 rs2276405. Our data support that AIM2 rs2276405 may be associated with mild‐moderate and sporadic psoriasis and might contribute to the complexity of clinical feature of psoriasis.