The Impact Of Family History Of Psoriatic Arthritis On Disease Characteristics And Genetic Study Of The Family In Chin

ObjectivesPsoriatic arthritis(PsA)is a chronic inflammatory joint disease closely related to psoriasis or a family history of psoriasis.Due to the heterogeneity of PsA,it can cause a variety of adverse effects,including joint dysfunction,deformity,and visible psoriatic skin lesions,resulting in decreased quality of life and increased psychological stress.So far,a number of studies have reported the disease characteristics of PsA cohorts in different countries and regions,and growing evidence has confirmed the familial aggregation tendency of PsA.However,data from large cohorts of PsA in Chinese patients are lacking.The aim of this study was to introduce the profile of Chinese PsA patients,and according to subgroup analysis of family history,to explore the impact of family history on clinical features of PsA.MethodsAs a national,multi-center platform,the Chinese REgistry of Psoriatic ARthritis(CREPAR),relying on the Chinese Rheumatism Data Center(CRDC),a clinical research and translational medicine platform,was established in December 2018.Based on CREPAR,data were collected,including demographic information,PsA clinical data,laboratory tests,disease assessment,and treatment strategies of PsA patients recruited on the platform from December 2018 to June 2021.Patients were divided into two groups according to with or without family history(defined as psoriasis or PsA in three generations of relatives)and their disease characteristics were compared.The impact of having the family history of psoriasis or PsA on disease characteristics of PsA were analyzed using Logistic regression analysis.ResultsA total of 1074 PsA patients were enrolled in this study.The study demonstrated that polyarthritis was the most common pattern of joint involvement.The occurrence of psoriasis before arthritis was more common.In addition to the skin and peripheral joints,among the other extra-articular manifestations,the most frequent extra-articular manifestation was nail changes.The frequency of axial involvement,enthesitis,and dactylitis was similar,and uveitis and enteritis were relatively rare.In terms of therapeutic drugs,conventional synthetic disease-modifying anti-rheumatic drugs were the most common application.Regarding the usage of biological agents,tumor necrosis factor antagonists was used more frequently.As for family history,313(29.1%)patients had a family history of psoriasis or PsA.Compared with no family history,patients with positive family history exhibited earlier age of onset both at psoriasis and PsA,and also,they reported higher frequency of enthesitis and nail involvement.When analyzing the variables after adjusting for confounding factors,having family history of psoriasis or PsA was associated with a higher proportion of female gender(OR 1.514,95%CI 1.0882.108,P=0.014),younger age at psoriasis onset(OR 0.971,95%CI 0.955-0.988,P=0.001),higher frequency of positive human leukocyte antigen-B27(OR 1.625,95%CI 1.089-2.426,P=0.018),higher percentage of enthesitis(OR 1.393,95%CI 1.005-1.930,P=0.046)and nail involvement(OR 1.424,95%CI 1.007-2.013,P=0.046),and higher proportion of hyperlipidemia(OR 2.550,95%CI 1.506-4.317,P=0.000)in PsA patients.ConclusionsThis is the first largest national multicenter cohort of Chinese PsA patients.Based on CREPAR,the characteristics of Chinese PsA patients were summarized,and the disease heterogeneity of PsA was confirmed.In addition,the study demonstrated that family history has a significant impact on both the clinical phenotype and disease activity of PsA patients.ObjectivesPsoriatic arthritis(PsA)is a chronic joint disease with various clinical features,including cutaneous lesions and inflammatory arthritis.Due to the lack of timely treatment,it may cause joint swelling,pain,dysfunction,and the visibility of skin lesions.The above symptoms are prone to recurring attacks,which brings huge impact and heavy burden to patients.However,the pathogenesis of the disease remains to be clarified.Therefore,it is of great significance to carry out genetic research on PsA for advancing understanding of PsA disease and formulating better treatment strategies.Some studies have reported that multiple genes were associated with PsA,and these genes can partially explain the heterogeneity of the occurrence and clinical manifestations of PsA.However,as a disease with a familial aggregation tendency,PsA has limited family-based genetic studies.Therefore,this study was aimed to explore the causative genes of this disease by performing single-nucleotide polymorphism(SNP)array and whole-exome sequencing(WES)analysis on PsA pedigrees.MethodsBased on the previous CREPAR cohort,peripheral blood was collected from 4 PsA pedigrees samples and DNA was extracted.SNP array analysis included data quality control and data analysis using linkage analysis.Furthermore,the samples were analyzed by WES,which included data filtering,alignment to the reference genome,SNP detection,Indel analysis,and database annotation.Then,Mendelian dominant and recessive inheritance patterns were further used to screen potential pathogenic genes.Enrichment analysis was performed according to the screened potential mutant harmful genes.ResultsAccording to LOD>2,in the Mendelian dominant model,the Multipoint family linkage analysis showed that rs1536337-kgp8081307 on chromosome 10 in the F1 family was a significant linkage locus.In the WES data analysis,according to the mutant allele frequency(MAF)<0.01,55 genes with potential pathogenic mutations were found,among which C2orf80 and TRPM6 gene mutations can lead to loss-of-function mutations,and others were missense mutations.Further application of enrichment analysis,GO functional enrichment analysis demonstrated that some biological process related to PsA were enriched,such as the regulation of canonical Wnt signaling pathway(3/55,P=0.036).In addition,KEEG pathway enrichment found that NF-kappa B,nucleocytoplasmic transport,and axon guidance were enriched.ConclusionsBased on modern genetic testing technology,this study provides direction and basis for genetic research of PsA,especially the location of pathogenic genes.