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.

Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies

“…Marneros and colleagues (23) studied two families with an autosomal-dominant inheritance pattern of keloids and identified linkage to chromosome 7p11 and chromosome 2q23 for the African and Japanese family, respectively. Brown and colleagues (24) found a genetic association between HLA-DRB1*15 status and the risk of developing keloid scarring in white individuals. Also, carriers of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 have been reported to be have an increased risk of developing keloid scarring (24).…”

“…Brown and colleagues (24) found a genetic association between HLA-DRB1*15 status and the risk of developing keloid scarring in white individuals. Also, carriers of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 have been reported to be have an increased risk of developing keloid scarring (24). Keloid growth may also be stimulated by various hormones, as indicated by some studies in which results have suggested a higher incidence of keloid formation during puberty and pregnancy, with a decrease in size after menopause (18,25,26).…”

Comprehensive Review of Keloid Formation

“…they identified linkage to chromosome 2q23 (maximal two-point LOD score of 3.01) for the Japanese family. The African-American family showed evidence for a keloid susceptibility locus on chromosome 7p11 (maximal two-point LOD score of 3.16) [34]. Brown and colleagues found a genetic association between HLA-DRB1*15 statuses and the risk of developing keloid scarring in white individuals [35].…”

The Incidence of Postoperative Flare Reaction and Tissue Complications in Dupuytren's Disease Using Tension-Free Immobilization

“…Dupuytren's disease is a fibroproliferative disorder that is clinically and pathophysiologically unique and is characterized by normal tissues becoming diseased. While the underlying etiology remains elusive, it has been established that Caucasian males of Northern European descent with a family history of the disease exhibit a high genetic susceptibility [5]. The genetic code, molecular signals, and cellular changes that lead to the fibroblastic disease in Dupuytren's disease, however, are currently being investigated [8,23].…”