The DDR gene located on chromosome region
The DDR1 gene, located on chromosome region 6p21.33, encodes a transmembrane tyrosine kinase receptor involved in melanocyte anchoring through binding to collagen IV (Silva de Castro et al., 2010). So far, only three studies have been conducted on the association between DDR1 polymorphism and the risk of developing vitiligo (Birlea et al., 2011; Kim et al., 2010; Silva de Castro et al., 2010), showing controversial results. The variations in the results are attributed to the ethnic differences resulting in various DDR1 BV6 distributions. Silva de Castro et al. in their family-based and case-control study conducted in Brazilian context, found a statistically significant association between the risk of developing vitiligo and DDR1 (rs2267641) polymorphism. They identified the risk allele of C and interestingly, they found that the risk of developing vitiligo was strongly dependent on age (Silva de Castro et al., 2010). Another study carried out in the Korean context, showed an association between the risk of developing vitiligo and DDR1 variants, although the results were not found to be robust in case of performing multiple testing corrections (Kim et al., 2010; Tarlé et al., 2014). In contrast, Birlea et al. in their study failed to replicate the same association; however, the authors did not evaluate study sample stratified based on age of onset of vitiligo (Birlea et al., 2011; Tarlé et al., 2014). The results of the present study confirm the results obtained from the study on the Brazilian population by demonstrating a strong relationship between the DDR1 gene polymorphism and the risk of developing vitiligo. The results of the stratified analysis revealed a significant correlation between the DDR1 CC genotype and the early onset of vitiligo, which was completely in agreement with those obtained in the study by Silva de Castro et al. It appears that the results of the present study confirm the age-dependent role of DDR1 CC genotype in early onset of vitiligo. Moreover, the findings of the present study suggest that the DDR1 CC genotype was associated not only with the clinical type of vitiligo, but it was also associated with the absence of family history of autoimmune disorders. These correlations were not evaluated in the study conducted on the Brazilian population. The genetic basis of vitiligo is deeply intertwined with the genetic basis of various other autoimmune diseases with which vitiligo is epidemiologically associated. On the one hand, many of the vitiligo susceptibility genes have also been shown to be associated with these autoimmune diseases. On the other hand, a higher frequency of the vitiligo-associated autoimmune diseases has been observed in first-degree relatives of vitiligo probands who did not themselves have vitiligo (Spritz and Andersen, 2017). In the present study, the results showed an association between both evaluated genes and development of autoimmune diseases not only in the patients themselves but also in their first-degree relatives. These findings support that, vitiligo share at least some of its genetic underpinnings with autoimmune diseases and propose a probable association between the adhesion deficit involved in vitiligo and autoimmune disorders. In this study, the substantial evidence in favour of the association between the risk of developing vitiligo and CDH1 and DDR1 genes polymorphisms reported in previous studies was confirmed. However, the small sample size was considered to be a limitation of this case-control study, and it should not be ignored while interpreting the results. This caution should be taken especially in subgroup analysis, in particular, the analysis of clinical type of vitiligo. Aside from this limitation, the present study has the strength regarding the well-matched cases and controls population. Moreover, the detailed patient information collected in the current study allowed subgroup analysis to be done based on eight different characteristics of the vitiligo patients, not only within the subjects in case group but also between the case and the control groups.