Acta Dermato-Venerelogica Issue No 7, 2017 97-7CompleteContent | Page 26

862 SHORT COMMUNICATION Parent-of-origin Effect in Alopecia Areata: A Large-scale Pedigree Study Silke REDLER 1,2 , F. Buket Ü. BASMANAV 2 , Bettina BLAUMEISER 3 , Natalie GARCIA BARTELS 4 , Gerhard LUTZ 5 , Aylar TAFAZZOLI 2 , Roland KRUSE 6 , Hans WOLFF 7 , Markus BÖHM 8 , Ulrike BLUME-PEYTAVI 4 , Tim BECKER 9,10 , Markus M. NÖTHEN 2,11 and Regina C. BETZ 2 Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, University of Düsseldorf, Universitätsstr. 1, DE-40225 Düsseldorf, Institute of Human Genetics, University of Bonn, Bonn, Germany, 3 Department of Medical Genetics, University of Antwerp, Antwerp, Belgium, 4 Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, 5 Hair & Nail, Dermatological Practice, Wesseling, 6 Dermatological Practice, Paderborn, 7 Department of Dermatology, University of Munich, Munich, 8 Department of Dermatology, University of Münster, Münster, 9 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, 10 German Center for Neurodegenerative Diseases (DZNE), and 11 Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. E-mail: [email protected] 1 2 Accepted Mar 22, 2017; Epub ahead of print Mar 28, 2017 Alopecia areata (AA) is a common hair loss disorder of autoimmune origin. Research suggests that the aetiology of AA involves both genetic and environmental factors. Several genetic risk loci have been identified (1–4). In the general population, the estimated lifetime risk of AA is 1–2%, with similar rates being reported in both sexes (5, 6). Several studies have reported familial clustering in patients with AA (7–9). However, many of these studies involved limited sample sizes. Moreover, only a few studies have reported rates of affected individuals for specific degrees of relatedness (7, 9, 10). In a previous report, our group presented comprehensive data on the pattern of familial aggregation in 206 AA families. In this cohort, we found a frequency of 5.5% for first- degree relatives, and approximately 7% for parents (7). In other AA cohorts, rates of affected individuals as high as 10% have been reported in parents (9, 10). These high rates indicate a parent-to-child transmission of genetic susceptibility variants. However, to our knowledge, no study to date has specifically investigated a pa rent-of- origin effect in AA. A parent-of-origin effect is present if the disease is inherited more frequently from either the maternal or the paternal side, or if phenotypic expression differs depending on whether the disease is inherited from the mother or the father. A parent-of-origin effect points to specific molecular mechanisms (e.g. genomic imprinting), which may suggest directions for follow-up studies. Epidemiological and molecular genetic studies have reported parent-of-origin effects in several complex autoimmune disorders, including conditions displaying comorbidity or genetic overlap with AA, such as multiple sclerosis, psoriatic arthritis, and inflammatory bowel disease (11–14). The aim of the present study was to investigate a pos- sible parent-of-origin effect in AA. METHODS Systematic analysis was performed in 2,230 3-generation pe- digrees, drawn from our previously reported and clinically well- characterized Central European AA sample (Table I). Information concerning the rates of affected individuals of parents, other doi: 10.2340/00015555-2658 Acta Derm Venereol 2017; 97: 862–863 Table I. Data on the present 2,230 3-generation Central European alopecia areata (AA) pedigrees Overall sample Females Males First-degree relative with AA Sibling/child Mother Father Second-degree relative with AA n Frequency % 2,230 1,640 590 291 145 79 66 212 73.54 26.46 13.05 6.55 3.54 2.96 9.51 first-degree relatives and second-degree relatives was obtained in interviews with all 2,230 patients with AA. For 206 of these pa- tients, a direct interview with parents was also conducted. Ethical approval was obtained from the respective ethics committees and informed consent from all of the patients. RESULTS A total of 145 of the 2,230 patients with (6.5%) reported having one affected parent: mother (n = 79; 54.5%) or father (n = 66; 45.5%). This is not suggestive of preferen- tial transmission from either the paternal or the maternal side (p = 0.319). None of the patients reported having 2 affected parents. In a subsequent step, we investigated whether sex-specific transmission patterns (maternal vs. paternal inheritance) may lead to dissimilarities in AA phenotypic expression. For this purpose, we sub- grouped our data according to disease severity and age of onset. Disease severity was defined according to AA subphenotype in the patient: patients with patchy AA were classified under the category “mild phenotype”; and patients with alopecia totalis or alopecia universalis were classified under the category “severe phenotype”. Of the 79 patients with an affected mother, 40 displayed severe AA. This proportion did not differ significantly from that observed in patients with an affected father (28 of 66 patients; p = 0.324). Similarly, no significant difference was found between the 2 groups in terms of the proportion of patients with an early age of onset (< 20 years) (38/79 vs. 30/66; p = 0.751). These data suggest that a parent-of-origin effect in the phenotypic expression of AA is unlikely. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.