| Objective:To explore the association between HLA-B,HLA-DR gene polymorphism and systemic lupus erythematosus(SLE)in Han population of Yunnan Province,and the relationship between the gene polymorphism and clinical indexes in SLE patients.METHODS:We recruited 116 SLE patients in Department of Rheumatology and Immunology in First Affiliated Hospital of Kunming Medical University from September 2015 to September 2017.They all met the 2009 American Institute of Rheumatology(ACR)Classification criterion of SLE.They were Han population of Yunnan province.We collected blood routine,urine routine,24h urine protein quantitative,complement,autoantibodies,lymphocytes,cytokines,SLE disease activity degree(SLEDAI)and other related clinical indexes.118 health controls(HC)of Han population were recruited.The HLA-B locus and DR locus genotypes and serotypes of the SLE patient and HC were detected by using the oligonucleotide probe method(PCR-SSO).We compared the differences of allele frequency and serotype frequency between SLE patients and HC.We analyzed correlations between susceptibility genes and clinical indicators of SLE patients.We further analyzed the haplotype differences HLA genes in SLE patients and HC group.Results:1.Genotyping results:(1)A total of 34 alleles were detected in the HLA-DR locus,of which the HLA-DRB1*08:03 allele frequency was significantly higher in the SLE group than in the HC group(17.26%vs.9.32%,P=0.016,OR 1.966;95%confidence interval(CI)1.125-3.433),and 24h urine protein in HLA-DRB1*08:03 positive group was significantly lower than HLA-DRB1*08:03 negative group(1.93±2.830 vs.3.55±4.556,P=0.03);the HLA-DRB1*11:01 allele frequency was significantly lower in the SLE group than in HC group(0.44%vs.4.66%,P=0.004,OR 0.089,95%CI 0.011-0.694);(2)A total of 53 alleles were detected at B site,The frequency of HLA-B*46:01 allele was significantly lower in the SLE group than in HC group(9.63%vs.16.17%,P=0.022,OR=0.519,95%CI 0.294-0.914),HLA-B*15:18 allele frequency in the SLE group was significantly lower than the HC group(0%vs.1.70%,P=0.046,OR 0.983,95%CI 0.967-0.999).2.Serotyping results:(1)A total of 15 serotypes were detected in HLA-DR locus,among which the HLA-DR8 serotype SLE group was significantly higher than the HC group(19.03%vs.9.75%,P=0.006,OR 2.118,95%Cl 1.231-3.646).HLA-DR8 serotype was positively correlated with anti-Sm-D1 antibody and SLEDAI(P=0.037,OR 2.429,95%CI 1.042-5.662;P=0.000,OR 10.528,95%C1 2.986-37.120;respectively).SLE group serotypes HLA-DR11,DR12 were significantly lower than the HC group(0.88%vs.5.08%,P=0.008,OR 0.163,95%CI 0.036-0.737;10.62%vs.17.37%,P=0.029,OR 0.551,95%CI 0.321-0.947;respectively).(2)A total of 33 serotypes were detected in HLA-B loci,among which the HLA-B46 serotype of SLE group was significantly lower than the HC group(9.63%vs.16.10%,P=0.025,OR 0.526,95%CI 0.298-0.928).The HLA-B13 serotype in SLE group was significantly higher than the HC group(10.55%vs.4.66%,P=0.04,OR 2.153,95%CI 1.019-4.548).3.The relationship between HLA serotype and lymphocyte and cytokine:The serum level of IL4 in HLA-B13 serotype positive group was significantly higher than that in HLA-B13 serotype negative group(1.573±0.474vs1.32±0.436,P=0.027).The absolute value of CD4+ T lymphocytes in the HLA-B13 serotype positive group was significantly higher than that in the HLA-B13 serotype negative group(531.5±280.5 vs.320.6±255.7,P=0.006);The absolute value of B cells in the HLA-B13 serotype positive group was significantly higher than that in the HLA-B13 serotype negative group(295.5± 175.6 vs.173.0±161.4,P=0.045).4.The frequency of HLA-B and HLA-DR locus haplotype B*13:01/DR*15:01 in the SLE group was significantly higher than that in the HC group(P= 0.04).Conclusions:(1)This study suggested that the HLA-DRB1*08:03 allele,HLA-DR8 serotype and HLA-B13 serotype were related to SLE in Han population of Yunnan Province.While alleles HLA-DRB1*11:01,HLA-B*46:01 and serotypes HLA-DR11,DR12 and B46 might play a protective role in the SLE of Yunnan Han population.(2)HLA-DRB 1*08:03 allele might be associated with renal involvement in SLE;HLA-DR8 serotype was associated with anti-Sm-D1 antibody and might affect the severity of the disease;HLA-B13 serotype was associated with lymphocytes and cytokines.(3)The pathogenesis of SLE was not only related to single HLA gene,but also possibly related to the combination of certain HLA genes,Haplotype B*13:01/DR*15:01 might be associated with the onset of SLE in Han population of Yunnan province,and might become a susceptible genetic marker for SLE. |
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