MOLECULAR TYPING OF HLA-B*27 SUB-ALLELES REVEALS AN ASSOCIATION WITH ERAP1 AND DISEASE SUBSET OF ANKYLOSING SPONDYLITIS IN NORTH-INDIAN (KASHMIR) POPULATION

Background: Human Leukocyte Antigen(HLA)-B*27 is significantly linked to Ankylosing spondylitis(AS) and its presence aids in the diagnosis of the disease. Identification of HLA-B*27 allele plays an important role in the clinical monitoring,diagnosis and therapy of this spondyloarthropathy because of high HLA polymorphism and differential contribution of alleles and molecules encoded by them. HLA-B*27 is also present in general population 7-8%.We evaluated the presence and correlation of various HLA-B*27 alleles with clinical parameters and ERAP1 (SNPs rs27434, rs27529 and rs26510) of Ankylosing spondylitis in Kashmiri Population. Methods: This study involved total 200 cases (100 Ankylosing Spondylitis patients and 100 healthy controls). Genomic DNA was extracted by phenol-chloroform method. All subjects were genotyped for HLA-B*27 subtyping by Polymerase Chain Reaction(PCR)-Sequence Specific Primer(SSP) method. Result: HLA-B*27 were present in 90% of cases and in 20% of controls OR 36.0(15.91-81.48)P= <0.0001. HLA-B*27:02 OR 9.12(2.63-31.6) p=<0.0001, CAFRW OR 12.61(4.73-33.9)p= <0.0001 and HLA-B*27+CAFRS OR 45.07(2.64-759.4)p=0.0001 were showing significant association with AS disease. Conclusion: The current study indicates that a majority of Kashmiri AS patients are associated with HLA-B*27 alleles. In addition we found that HLA-B*27 associated AS patients presented with more severe axial manifestation.