| Objective1.To clarify the correlation between the genetic variation of the ERAP1 gene region and psoriasis vulgaris in the Han population of Inner Mongolia.2.Using HLA-C*0602 stratified analysis to explore the correlation between its interaction with ERAP1 and susceptibility to psoriasis vulgaris in the Han population of Inner Mongolia.3.Stratified according to the age of onset（early onset≤40 years old or late onset>40 years old）to explore the correlation between genetic mutations in ERAP1 and psoriasis vulgaris in Han population of Inner Mongolia.4.Stratified analysis with or without family history to explore the correlation between genetic mutations in ERAP1 and psoriasis vulgaris in the Han population of InnerMongolia.MethodsThis experiment is divided into two stages:primary screening sequencing and verification sequencing.The preliminary screening sequencing research object included 142 cases of psoriasis vulgaris and 100 healthy controls without psoriasis,and the verification sequencing research object contained 1030 cases of psoriasis vulgaris and 956 healthy controls.The peripheral blood（anticoagulated whole blood）of the study subjects was collected-80℃and stored for later use to extract DNA samples.Primary screening sequencing Second-generation sequencing was used to sequence the 27 exons of ERAP1 to screen for significant mutation sites.Verify that the sequencing has a significant number of mutation sites in the primary screening sequence and 18 previously reported mutation sites.The next-generation sequencing method and sequence-specific primer polymerase chain reaction detection were used to analyze the genetic variation of ERAP1 and psoriasis.The relationship between disease and whether HLA-C*0602 has interaction with ERAP1.The combined analysis of the data in the initial screening stage and the verification stage was performed using the Cochran-Mantel-Haenszel（CMH）method.The age of onset（≤40 years old and>40 years old）and family history were analyzed by stratified analysis and the relationship between psoriasis vulgaris.All genetic variation typing data quality control,alleles,and gene rates were compared using PLINK 1.07 software.The minimum allele frequency（MAF）was compared by chi-square test（χ2）,and the odds ratio（OR）of the smallest allele was calculated.)and its 95% confidence interval（95%CI）.All statistical tests use a two-sided probability test,withα=0.05 as the test standard,and P<0.05 as the difference is statistically significant.Results1.In the initial screening stage,after sequencing the 27 exons of the ERAP1 gene,a total of 157 genetic mutations were found.After quality control and screening（removal of genetic variations that do not meet the HWE balance,removal of alleles with frequencies less than 0.01）Variation),a total of 85 genetic variations were included in the statistical analysis.Chi-square test revealed 13 genetic variations that were associated with psoriasis（P<0.05）,respectively rs27980,rs27042,rs27044,rs469876,rs469783,rs469758,rs26510,rs27434,rs998509,rs766222717,rs3734016,rs151949,rs77311599.A total of 18 genetic variants were typed in the verification phase,and a total of 12 genetic variants were associated with psoriasis.The combined analysis of the data from the preliminary screening stage and the verification stage showed that there were 12 mutation sites related to the ERAP1 gene of psoriasis vulgaris in the Han population of Inner Mongolia,which were:rs27980＿G（P=0.002,OR=0.82）,rs469876＿G（P=0.013,OR=0.84）,rs77311599＿T（P=0.008,OR=0.63）,rs998509＿A（P=0.003,OR=0.77）,rs766222717＿C（P=0.001,OR=0.75）,rs3734016＿T(P=4.56×10-04,OR=0.73),rs27044＿G（P=0.003,OR=1.20）,rs469783＿C(P=2.57×10-05,OR=1.32),rs469758＿C(P=8.50×10-06,OR=1.33),rs26510＿C(P=8.44×10-06,OR=1.33),rs30187＿T(P=3.94×10-04,OR=1.25),rs27434＿A（P=0.002,OR=1.22）.And rs27042＿A,rs2287987＿C,rs17482078＿T,rs26653＿G,rs10050860＿T,rs151949＿T had no significant correlation with psoriasis（P>0.05）.2.HLA-C*0602 negative and positive for stratified analysis of the correlation between ERAP1 genetic variation and patients with psoriasis vulgaris in the Han population of Inner Mongolia.The results showed that when HLA-C*0602 was positive,rs469783＿C（P=0.036,OR=1.29）、rs469758＿C（P=0.030,OR=1.31）、rs26510＿C（P=0.047,OR=1.28）have a significant correlation with psoriasis,and no significant correlation when negative.3.Stratified analysis based on whether there is a family history of psoriasis.The results showed that a total of 8 genetic mutations in ERAP1 were significant in patients with a positive family history in the allele frequencies of the case group and the control group.The differences were:rs469783,rs469758,rs30187,rs26510,rs27434,rs998509,rs944222717,rs3734016（P<0.05）.In patients with negative family history,there were 9 genetic variants of EARP1 that had significant differences in allele frequencies between the patient group and the control group,respectively:rs27044,rs469783,rs469758,rs30187,rs26510,rs77311599,rs27434,rs766222717,rs3734016（P<0.05）.4.According to the time of onset,it was divided into early-onset（onset age≤40 years）and late-onset psoriasis（onset age>40 years）and grouped（including 519 cases of early-onset psoriasis and 369 cases of late-onset psoriasis）.In early onset,there were 8 genetic mutations in ERAP1 that were associated with psoriasis,respectively:rs27044,rs469783,rs469758,rs30187,rs26510,rs27434,rs766222717,and rs3734016（P<0.05）.There are two genetic variants of ERAP1 that are associated with the disease in advanced disease,rs27980 and rs3734016,respectively（P<0.05）. Conclusions1.Through two-stage association analysis,12 genetic mutations in the ERAP1 gene region are associated with psoriasis vulgaris in the Han population of Inner Mongolia.Among them,rs27044＿G,rs469783＿C,rs469758＿C,rs26510＿C,rs30187＿T,and rs27434＿A are the risk of psoriasis.Factors;rs27980＿G,rs469876＿G,rs77311599＿T,rs998509＿A,rs766222717＿C,rs3734016＿T are protective factors for the onset of psoriasis.2.There may be an interaction between HLA-C*0602 and ERAP1 gene,which affects the risk of psoriasis vulgaris in Han people of Inner Mongolia.In HLA-C*0602 positive samples,the genetic variants rs469783＿C,rs469758＿C,and rs26510＿C of ERAP1 are associated with psoriasis in the Han population of Inner Mongolia and are the risk of factors of psoriasis.3.The results of stratified analysis according to the age of onset suggest that there are differences in the genetic variation of ERAP1 gene associated with early-onset and late-onset psoriasis vulgaris.rs766222717＿C is a protective factor only in early-onset psoriasis,rs27044＿G,rs469783＿C,rs469758＿C,rs30187＿T,rs26510＿C,rs27434＿A are only risk factors in early-onset psoriasis.rs27980＿G is a protective factor only in late-onset psoriasis.rs3734016＿T is a protective factor for psoriasis in both early and late hairstyles.4.The results of stratified analysis according to family history suggest that the genetic variation associated with psoriasis vulgaris patients with and without family history is the same or different:rs469783＿C,rs469758＿C,rs30187＿T,rs26510＿C,rs27434＿A,rs766222717＿C,rs3734016＿T or not Family history was associated with psoriasis.rs998509＿A was only related to psoriasis with family history;rs77311599＿T and rs27044＿G were only related to psoriasis without family history. |
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