Rheumatic heart disease (RHD), a chronic condition, results from rheumatic fever—an inflammatorydisease caused byuntreatedstreptococcalinfections. The human leukocyte antigen (HLA) system, specifically the HLA DRB1 gene, has been strongly associated with the development and progression of RHD. Certain HLA DRB1 alleles, such as HLA-DRB1*01 and *04, have been identified as major genetic risk factors for RHD. These alleles playa crucialrole in the activation of the immune systemand the generation of auto antibodies, contributing to the pathogenesis ofRHD. Understanding the connectionbetweenHLADRB1 and RHD canprovide insights into disease mechanisms and potentially guide personalized treatment approaches. This research employed a case-control study design to investigate the significance of HLA DRB1 in rheumaticheartdisease(RHD).Atotalof40participantswereincluded inthestudy,consistingof 30 female and 10 male individuals. The participantswererecruited froma specialized cardiology clinic,basedontheirdiagnosisofrheumatoidarthritis(RA)withorwithoutRHD.GenomicDNA was extracted from peripheral blood samples collected from each participant. The genotyping of HLADRB1alleleswasperformedusingpolymerasechainreaction(PCR)amplificationfollowed by sequence-specific oligonucleotide (SSO) hybridization or allele-specific PCR. These techniques allowed for the identification of specific HLA DRB1 alleles in each participant.