The Genetic Epidemiology of Vitiligo in Chinese
Vitiligo (OMIM: #193200) is an acquired, sometimes familial depigmentary disorder, presenting white patches and/or gray hair of the skin and hair that results from selective destruction of melanocytes. To date, the pathogenesis of vitiligo is unknown although there are many theories about its etiology, including self-destructive, biochemical, neural, autoimmune, and genetic hypotheses. In resent years, genetic contributions were revealed as the most important causative factor of vitiligo. Moreover, scientists hold the other hypotheses of vitiligo began to seek for supporting evidence from genetics and something were found. Because of the different genetic background, it is unlikely that all vitiligo patients share an inheritant basement between races or ethnic groups. Furthermore, it is also unknown whether all kinds of vitiligo are consistent with each other in respect of the pathogenesis, as we know vitiligo is clinically classified as being focal, vulgaris, universal, acrofacial, and segmental. In most previous studies, clinical presentations of vitiligo were often omitted, which might draw incorrect conclusions on vitiligous genetics. Up to date, no study has been conducted to explore the etiology and pathogenesis of vitiligo based on a large scale of genetic epidemiologic survey.The aims of the present study are to explore the mode of inheritance of vitiligo and evaluate the heritability of vitiligo in Chinese through a genetic epidemiological survey on a large scale. At the same time, we will attempt to illuminate the onset characteristicsof vitiligo, describe the clinical profiles and the developing laws of vitiligo, probe into the causations of vitiligous familial aggregation and as a pilot study, analyze a series of environmental factors potentially associated with vitiligo.Through collaboration of multi-clinical centers, we collected eligible data from 3742 vitiligo patients and their pedigrees by a uniform questionnaire. All the data were inputted into a database set up by Epi Info 5.0 package. After proper transformation, the data were statistically analyzed by statistic package of social science (SPSS, version 10.0), statistic analysis of genetic epidemiology (SAGE, version 3.1) and Falconer’s method in order to describe the profiles of vitiligo, model the mode of inheritance and evaluate the heritability of vitiligo. Binary logistic regression was used to estimate the associated risk of potential environmental factors underling vitiligo.Among the large cohort of vitiligo patients, 1273 (34.0%) individuals had focal, 1565 (41.8%) had vulgaris, 208 (5.6%) had universal, 322 (8.6%) had acrofacial, and 374 (10.0%) had segmental vitiligo. The mean age of onset was 18.88 ± 0.21 years old with a range from 1 to 72 years. No difference was identified with respect to the onset age of vitiligo between males and females (P > 0.05). However, different clinical types of vitiligo didn’t share a common onset age in males (P < 0.001). The onset age of universal vitiligo (23.71 yr) was much greater than that of segmental vitiligo (14.22, P < 0.01). The difference between onset ages of different clinical types of vitiligo was not significant (P = 0.088) in the female patients.The most initial site of vitiligo was the head and the least was the feet. The frequencies of initial affected sites were not coincident between males and females (P < 0.001). The top progress rate (83%) accompanied the vitiligo initially affected the perineum. Althouth the most initial site was the head, vitiligo arised from the head was more stablethan the others. After a mean duration of 3 to 5 years from the onset, 1629 (43.5%) patients' clinical types transformed and 1613 (99.0%) of them aggravated progressively. There was no transformation between acrofacial vitiligo and segmental vitiligo, which was suggestive of a markedly different pathogenesis between them.Out of the 3742 vitiligo patients, 299 (7.99%) cases reported a history of associated (autoimmune) diseases. The significantly elevated complications among this large cohort of vitiligo were rheumatic arthritis, ichthyosis, chronic urticaria, alopecia areata, and halo nevus (P < 0.05) compared to the frequencies of them in the general populations. Unbelievably, the frequencies of hypothyroid disorders were lower (P < 0.05) than those in the general populations. Overall, compared with male patients, more female patients (P = 0.014) were complicated by an associated disease.In the set of vitiligo patients, 538 (14.4%) cases reported a positive family history of vitiligo. As revealed by the analysis of one-way analysis of variance (ANOVA), the onset age of vitiligo was affected not only by the clinical presentations but also by the family history of vitiligo. Within the 3742 families, there were 404 (2.99%) out of 13523 first-degree relatives, 152 (0.39%) out of 39275 second-degree relatives, and 93 (0.23%) out of 41045 third-degree relatives of probands who were also afflicted with vitiligo. Mantel's trend chi-square tests displayed a significantly increased trend of developing vitiligo with increasing relatedness to the vitiligo patients (P < 0.001). A polygenic additive model was the best genetic model (P > 0.05) for focal vitiligo, vitiligo vulgaris, acrofacial vitiligo and segmental vitiligo with approximate 50% heritability in total revealed by complex segregation analyses. For universal vitiligo, the best model was an environmental model (P > 0.05).