Association Of The HLA-DRB1 Amino Acid Haplotypes With Rheumatoid Arthritis And Systemic Lupus Erythematosus In Yunnan

Rheumatoid arthritis(RA)and Systemic lupus erythematosus(SLE)are two common autoimmune diseases which the pathogenesis is not yet clear.Genetic and environmental factors are thought to contribute to the development of RA and SLE.More and more studies have confirmed the association of HLA-DRB1 gene with RA and SLE,but the relevant mechanism is not yet completely understood.HLA-DRB1 gene belongs to HLA class II gene,encodes the beta chain of HLA class II antigen,and participates in the process of antigen presentation.Recent studies have shown that the susceptibility of RA and SLE were associated to the amino acid types and haplotypes of HLA-DRB1 gene which position at antigen binding grooves,suggesting that the change of amino acid types in the peptide binding groove will affect the conformation of HLA-DRB1 molecule,which will affect the binding of HLA class II molecules to the antigen peptide.However,the susceptibility genes of RA and SLE are differences in different populations.Therefore,the HLA-DRB1 amino acid types and haplotypes associated with the susceptibility of RA and SLE need further validation.With a genome-wide association study(GWAS)in RA and SLE,many susceptibility locis were found,and the results shows that the susceptibility genes of RA was also important to SLE,suggesting that autoimmune diseases may have a similar genetic machanism.So this study wants to discuss whether the HLA-DRB1 amino acid types and haplotypes are associated with RA and SLE at Han population in Yunnan area,and whether the association of HLA-DRB1 amino acid types and haplotypes with RA and SLE is consistent or difference.To explore the association of HLA-DRB1 amino acid types and haplotypes with RA and SLE at Han population in Yunnan,and whether the association of HLA-DRB1 amino acid types and haplotypes with RA ans SLE were a similar genetic mechanism.In total of 256 RA patients and 218 controls;335 SLE patients and 255 controls Han in Yunnan,HLA-DRB1 amino acid types and haplotypes on positions 11,13,57,67,71 and 74 were determined by using Polymerase Chain Reaction sequencing based typing(PCR-SBR).According to the sequencing results,the HLA-DRB1 amino acid types at position 11,13,26,57,67,71,and 74 were obtained by comparing to the codons table.Analysing the association of HLA-DRB1 amino acid types and haplotypes with RA and SLE in a case-control study.The results were compared between the association of HLA-DRB1 amino acid types and haplotypes with RA and SLE,to explore the consistent or difference at the association of HLA-DRB1 amino acid types and haplotypes with RA ans SLE.Results:(1)The 11-V,11-L,13-H,13-F,57-S and 67-L of HLA-DRB1 gene were associated to the susceptibility of RA in Yunnan Han.11-S,13-S,71-E,74-R may play a protective roles.The amino acid position 26 of HLA-DRB1 gene is not associated to the susceptibility of RA.HLA-DRB1 amino acid haplotype(11-13-26)LFL and VHF are associated with the susceptibility of RA.SSF,SSY may play a protective role.HLA-DRB1 amino acid haplotype(11-71-74)LRA and VRA were RA-risk.SEA,SKR,SRA,SRE may a RA-protective.HLA-DRB1 amino acid haplotype(11-13-57-67-71-74)LFDLRA and VHSLRA were risk factors for RA.SSDFRA,SSDIEA,SSDLKR may play a protective roles.(2)the 11-P,13-R,26-Y,71-A,74-L of HLA-DRB1 amino acids were associated to the susceptibility of SLE in Yunnan Han.11-V,13-H,13-S,26-L,71-R,71-E,74-A may play a protective role.The amino acid positions 57 and 67 of HLA-DRB1 gene were not associated to the susceptibility of SLE.HLA-DRB1 amino acid haplotype(11-13-26)PRF and SGF are associated with susceptibility to SLE.SGL,SSF,VHF may play a protective role.HLA-DRB1 amino acid haplotype(11-71-74)PAA is a risk factor for SLE.SEA,SRA,VRA,VRE,DAE,GAQ,SAA,SAL may play a protective role.HLA-DRB1 amino acid haplotype(11-13-57-67-71-74)SGSIRL was a SLE-risk.VHDLRE,SSDIEA,SGVFRA,SGSIAL may a SLE-protective.(3)the susceptibility of RA and SLE were associated with the amino acid positions at 11,13,71,and the 74 of HLA-DRB1 gene.13-S,71-E,SSF(11-13-26),SEA(11-71-74),SRA(11-71-74)on RA and SLE play a protective role.However,11-V,71-R,VHF(11-13-26),VRA(11-71-74)may be a risk factor for RA,but play a protective role for SLE.The amino acid position 26 were associated to the susceptibility of SLE,but RA not.The amino acid positions at 57 and 67 were associated to the susceptibility of RA,but not with SLE.And the HLA-DRB1 amino acid types and haplotypes susceptibility of the RA and SLE were completely different.Conclusion:(1)In Yunnan Han,the susceptibility of RA and SLE were associated with HLA-DRB1 amino acid types and haplotypes.(2)The RA and SLE risk factors of HLA-DRB1 amino acid types and haplotypes were completely different.However,the amino acid types and haplotypes which play a protective factors of RA and SLE were partially consistent,suddesting that the mechanism of RA and SLE susceptibility associated with HLA-DRB1 gene may be similar,which is the specific amino acid type and haplotype at the antigen binding groove can bind self-antigen present to CD4+ T cell activate the immune response.(3)SNPs based ELB algorithm is a accurate,cost effective and high throughput method for imputing HLA-DRB1 amino acid haplotypes in given populations.The accuracy of the ELB method is associated with the number of amino acid analyzed.