Association Of Interleukin 22(IL-22) Gene Copy Number Variations And Ankylosing Spondylitis In Chinese Han Populations

Objective:1.To describe the distribution of IL-22 gene copy number in Chinese Han AS patients and healthy controls;2.To analyze the association of IL-22 CNVs and AS susceptibility;3.To explore the association of IL-22 gene CNVs and disease severity and the interaction between IL-22 CNVs and potential environment factors,providing clues for further clarifying the pathogenesis of AS;Methods:1.649 Chinese Han patients diagnosed with AS were consecutively enrolled from the Rheumatism and Immunity Clinic at the First Affiliated Hospital of Anhui Medical University from 2013 to 2016.A total of 628 healthy controls matching by sex and age were recruited from center blood stations at hefei city.5ml peripheral blood of all patients and controls were collected,at the same time,self-designed epidemiological questionnaire was used to gather demographic information of patients and controls,laboratory test results and clinical characteristics of the patients,and so on.2.DNA was collected from peripheral blood leukocytes by using a QIAGEN kit and stored at-80?C,the copy number of IL-22 gene was measured by AccuCopy^TM methods.3.The difference of quantitative data between the two groups was compared by t test,difference of qualitative data and distribution of IL-22 copy number between two groups were compared by ?² test,regression model was used to analysis the relation of gene CNVs and severity of disease,case-only design was used to analysis the interaction between gene CNVs and environment factors.P<0.05 was considered to be statistically significant,all statistical analyses were performed using SPSS version 16.0.Results:1.The distribution and difference of IL-22 gene copy number in Chinese Han AS patients and healthy controls: IL-22₁ gene copy number ranged from 1²,among patients,four persons have one copy?0.6%?,626 have two copy?99.4%?;among controls,three have one copy?0.5%?,592 have two copy?99.5%?,IL-22₂ gene copy number ranged from 1³,among patients,seven have one copy?1.1%?,612 have two copy?98.6%?,two have three copy?0.3%?;among controls,19 have one copy?3.2%?,573 have two copy?96.8%?,no people have three copy?0%?.There was no significant difference in IL-22₁ copy number distribution between case group and control group??²=0.092,P=1.000?,however,it is significant in IL-22₂ copy number distribution??²=7.760,P=0.01?.Considering the low mutation frequency of IL-22₂ 3 copy,only0.3% in patients,and 0% in the control,after removing it,the distribution difference was still statistically significant??²=6.223,P=0.013?.After stratified by sex,the difference was statistically significant in males??²=6.894,P=0.009?.2.Correlation analysis of IL-22 gene CNVs and severity of AS disease: regression analysis showed no association between IL-22 gene CNVs and disease activity?BASDAI?and disease function index?BASFI?.3.Interaction analysis between IL-22₂ gene CNVs and environment factors: compared with regular consumption of vegetables,the interactions between occasional consumption and IL-22 CNVs was significant?OR=8.93,95%CI=1.21-65.81,P=0.032?.No interaction was found between IL-22 gene CNVs and other environmental factors.Conclusion:The results showed IL-22 gene CNVs might be associated with AS susceptibility,the low copy number?= 1?was possibly the protective factor of AS;IL-22 gene CNVs was not associated with the disease severity of AS;the interaction analysis showed that vegetable consumption might have a combined action with IL-22 gene CNVs in AS.