Correspondence Association between estrogen receptor-a gene polymorphisms and dermatomyositis in Bulgarian patients Editor, The etiology of dermatomyositis (DM) is not clearly understood, but the existence of a strong genetic predispo- sition has been recognized. Environmental and hormonal factors are known to contribute towards the expression of the disease. Since DM affects women three times more often than men, the estrogens have been proposed as obvious candidates to explain the sexual dimorphism. 1 Estrogen acts through two nuclear receptors: estrogen receptor-a (ER-a), coded by ESR1, and estrogen receptor- b (ER-b), coded by ESR2. The PvuII P (C) and XbaI X (G) variants were found to lead to enhanced ER-a activ- ity 2,3 and elevated serum estradiol production. 4,5 Until now, there has been no study of the association of ESR1 XbaI x/X and PvuII p/P polymorphisms in DM. We investigated the frequencies of the XbaI x/X and PvuII polymorphisms in 34 patients with DM and 69 healthy control subjects. The work described in this letter was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. The study was approved by the local ethics committee at the Medical University of Sofia. The PvuII and XbaI polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) as previously described. 6 The ESR1 XbaI x/X and PvuII p/P polymorphisms appeared in linkage dysequilibrium (D′ = 0.84). No statistically significant difference in allele and genotype frequencies was found between patients and controls. Neither did stratification by gender lead to any statisti- cally significant differences. The predominant genotype in both groups was XxPp, followed by xxpp and XXPP; there were no statistically significant differences in their distribution. Thus, in the present study, we observed an association between the X allele and the XX + Xx genotypes (X, P = 0.03, odds ratio [OR] 2.9, 95% confi- dence interval [CI] 1.1–7.9; XX + Xx, P = 0.025, OR 6.1, 95% CI 1.2–30.1) and photosensitivity in DM patients. The P allele (P = 0.09, OR 2.2, 95% CI 0.8– 6.0) and PP + Pp genotypes (P = 0.057, OR 4.7, 95% CI 0.4–23.0) were also found predominantly among the photosensitive DM patients (Table 1). The combined genotypes containing at least two dominant alleles (XXPP, XxPp, XXPp) showed an association with photosensitivity in DM patients (P = 0.025, OR 6.1, 95% CI 1.2–30.1). Table 1 Analysis of frequencies of the ESR1 XbaI x/X and PvuII p/P polymorphisms and clinical parameters of dermatomyositis Genotype Dermatomyositis XbaI PvuII Clinical parameters xx (n = 11) Xx (n = 16) XX (n = 7) P-value pp (n = 10) Pp (n = 18) PP (n = 6) P-value Muscle weakness 9 (81.8%) 12 (75.0%) 6 (85.7%) 0.55 9 (90.0%) 13 (72.2%) 5 (83.3%) 0.3 Elevated muscle enzymes 8 (72.7%) 7 (43.8%) 4 (57.1%) 0.16 8 (80.0%) 7 (38.9%) 4 (66.7%) 0.07 EMG findings 6 (54.6%) 7 (43.8%) 6 (85.7%) 0.085 6 (60.0%) 9 (50.0%) 4 (66.7%) 0.33 Muscle biopsy findings 0 0 0 NS 0 0 0 NS Cutaneous disease 7 (63.6%) 13 (81.3%) 6 (85.7%) 0.2 7 (70.0%) 14 (77.8%) 5 (83.3%) 0.43 Photosensitivity 3 (27.3%) 11 (68.8%) 5 (71.4%) 0.025 3 (30.0%) 12 (66.7%) 4 (66.7%) 0.056 Immunological disease (Antisynthetase and anti-myositis specific antibodies) 4 (36.4%) 4 (25.0%) 0 NS 4 (40.0%) 3 (16.7%) 1 (16.7%) NS NS, not significant; EMG, electromyography. ª 2014 The International Society of Dermatology International Journal of Dermatology 2014 1