Positive association of HLA‐DRB1*15 with keloid disease in Caucasians

Abstract

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and concordance in identical twins suggest a strong genetic predisposition to keloid formation. The most polymorphic genetic system in all vertebrates is the major histocompatibility complex (MHC) also known as the human leucocyte antigens (HLA) system. The MHC has been shown to be strongly associated with numerous conditions. Of particular interest is the association of DR2 with dermal fibrotic diseases such as sarcoidosis. To investigate the aetiology of KD, we compared the HLA-DRB1 phenotype frequencies of Caucasoid patients with keloid scars against those observed in a control population (n = 537). A total number of 67 keloid cases were evaluated in the study. HLA-DRB1 alleles were determined in all cases and controls using a commercially available semiautomated reverse hybridization polymerase chain reaction sequence-specific oligonucleotide probes typing system. HLA-DRB1*15 phenotype frequency was higher in KD-positive Caucasians (38.8%) when compared with controls (20.9%) (corrected P = 0.017). We conclude that in Caucasians of Northern European origin, HLA-DRB1*15 is associated with risk of developing KD following injury. We have demonstrated for the first time that a genetic association exists between HLA-DRB1*15 status and the risk of developing keloid scarring in Caucasians. Our data suggest the possible involvement of an immunogenic component to KD although the exact mechanisms involved in MHC-driven abnormal fibrosis will require further investigation.