Polymorphic light eruption and the HLA DRB1*0301 extended haplotype are independent risk factors for cutaneous lupus erythematosus

Abstract

Recent evidence suggests that polymorphic light eruption (PLE) is an inherited photosensitivity disorder which may predispose to cutaneous lupus erythematosus (LE). In this study we examine the relative risk (RR) attributable to the presence of PLE, together with the effect of the major histocompatibility complex (MHC) in the development of cutaneous LE. Eighty-five Caucasian patients with annular subacute cutaneous LE (SCLE) and discoid LE (DLE) were recruited, together with 102 first degree relatives and 200 healthy local Caucasian controls. Symptoms suggestive of PLE were elicited in patients and relatives, and human leukocyte antigen (HLA) typing determined by PCR-SSP. Standard association analysis and family transmission disequilibrium testing (TDT) were then used to compare the HLA frequencies between groups. We found a significant (P < 0.05) association of the HLA A*01, B*08, DRB1*0301 extended haplotype with both SCLE and DLE and also significant association of DLE with the HLA A*03, B*07, DRB1*15 haplotype, with a possible protective effect in SCLE for HLA B*44 and DRB1*04 (P=0.002 and 0.001 respectively). Association was observed between PLE and cutaneous LE (P < 0.001), but not between PLE and any HLA allele. From these figures we estimate, for the general population, that the RR of developing SCLE given the presence of (a) PLE, (b) DRB1*0301 and (c) both PLE and DRB1*0301 is 3.37, 5.45 and 12.03, respectively. For DLE, equivalent RRs are 3.11, 2.15 and 6.94. In conclusion, these data imply the involvement of both PLE and HLA DRB1*0301 in the development of SCLE and DLE. They form a basis for examining the genetic architecture of photosensitivity, some aspects of which may be common to both cutaneous LE and PLE.