Investigation Of Major Histocompatibility Complex In Chinese Han Psoriatic Arthritis Population

BackgroundPsoriatic arthritis(Ps A)is a chronic autoimmune disease that it is primarily invading the skin(the psoriatic skin features commonly include epidermal hyperplasia,hyperkeratosis,parakeratosis,Munro's microabscesses and mixed dermal infiltrates,inducing by the interaction of keratinocytes and immune cells)and musculoskeletal system.Patients with Ps A usually have extensive phenotype with arthritis damage(include peripheral arthritis,finger pain,cystitis and axial disease),extra-articular manifestations(psoriatic skin and nails features)and the other organs involvement.In some cases that patients with Ps A without psoriatic skin features only have arthritis damage of finger pain similar to RA.Generally,only about 13% of patients with Ps A can be detected rheumatoid factor in the blood and synovial fluid,while more than 80% of RA patients can be detected Rheumatoid factor.In general,the patient's joint symptoms are accompanied by increased or reduced skin symptoms.The pathogenesis of Ps A is concealed,the development of the disease is progressive,and previous researches have shown that it is harmful to individual's health and life quality,and the patients with Ps A may have a higher risk to suffer from cardiovascular events.In the world population,the prevalence of Ps A is about 0.3%-1%,in western country,the prevalence rates are about 0.02%,0.42% and 0.25% respectively in Sweden,Italy and the United States,whereas there is a lower prevalence in the eastern country relatively,less than 0.00001% in Japan,ranging from 0.01% to 0.1% in Chinese population similar to other places.However,the pathogenesis of Ps A is not clear,it is generally believed that the disease with genetic heterogeneity,phenotypic complexity and racial differences is caused by polygenic genetic and environmental risk factors.In humans,HLA played an important role in the occurrence of many human diseases,including autoimmune diseases,infectious diseases and cancer.Genetic studies reveal that Ps A is associated with MHC,numerous of studies for HLA alleles had been performed.Some of these alleles played as protective role in pathological process,some confer susceptibility to Ps A.For instance,HLA-B*13 as a risk factor and HLA-C*03 as a protective factor had shown association with Ps A in European population,HLA-B*27:05 had embodied a significant association with Ps A in Brazilian and Irish.However,up to now,most of these studies were performed in Europeans,the study on Chinese Han population is few.ObjectiveFor the purpose of finding the new susceptible genes of Ps A in MHC in Chinese Han population and validating the existing Ps A-associated HLA alleles of other populations in Chinese Han population.Materials and methodsIn this case-control study,EDTA-anticoagulated venous blood samples were collected from 111 adult patients with Ps A and 207 healthy controls(HCs).Genomic DNA was extracted from peripheral blood lymphocytes.Extracted genomic DNA was amplified by PCR using locus-specific primers for each of the HLA-A,HLA-B,HLA-C and HLA-DRB1 loci based on the association between HLA and Ps A demonstrated in different populations.Quality check for the PCR amplification products that the sequencing quality value Q30 for all samples was not less than 92%.Filter incompatible reads,compared the products to primers and HLA database(IPD-IMGT/HLA 3.21.0,http://hla.alleles.org/alleles/index.html).then deep sequencing of overall sequencing of each sample had been performed by using software Blast+(https://blast.ncbi.nlm.nih.gov/Blast.cgi).Through aligned to HLA reference sequences and compared with HLA database by using software HLAminer v.1.3.1.The cases and HCs were performed to explore the significant association of HLA-A,HLA-B,HLA-C and HLA-DRB1 alleles with Ps A,by using logistic regression analysis of single and double precision levels analysis.Results:We found that the double allele frequency of HLA-A*01:01 was strikingly increased in the Ps A group compared with the HC group [P=5.5×10-4,odds ratio(OR)=3.35(1.69-6.66),95%CI 1.69-6.66].Meantime,HLA-A*01[P=5×10-5,OR=3.43(1.89-6.23)],HLA-B*13[P=4×10-6,OR=2.65(1.76-4.01)],HLA-B*27[P=7.5×10-4,OR=5.84(2.09-16.29)],HLA-B*57[P=5.8×10-5,OR=20.10(4.65-86.83)],HLA-C*06[P=1.9×10-12,OR=4.48(2.95-6.81)] and HLA-C*06:02[P=8.5×10-7,OR=3.80(2.23-6.47)] also had been demonstrated as risk alleles for Ps A,and HLA-C*03[P=2.1×10-4,OR=0.40(0.25-0.65)] as protective allele for Ps A in Chinese Han population.Conclusion:We found a new associated allele HLA-A*01:01 of Ps A in Chinese Han population,which hadn't been presented as a risk factor in the literature.The HLA-A*01:01 allele may be a risk factor in Ps A,which suggests the participation of autoimmunity in the pathogenesis of Ps A.Also,we verified that HLA-A*01,HLA-B*13,HLA-B*27,HLA-B*57,HLA-C*06 and HLA-C*06:02 were as risk alleles for Ps A,and HLA-C*03 as protective allele for Ps A in Chinese Han population which were basically consistent with the previous studies in other populations.The results extend the susceptibility HLA alleles of Ps A in Chinese Han population.