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.