Associations Between Functional Polymorphisms Of The Genes In FAS Apoptosis Way And Risk Of Vitiligo In Chinese Populations

Vitiligo is an acquired pigmentary disorder characterized by depigmentation of the skin and a loss of epidermal melanocytes. Various etiologic hypotheses have been suggested, for which the most compelling evidence involves a combination of environmental, genetic, and immunologic factors interacting to contribute to autoimmune melanocyte destruction.Fas, also known as TNFRSF6/CD95/APO–1, is a cell surface factor, and FasL, also known as TNFSF6/ CD95L, is a member of the tumor necrosis factor superfamily. Fas participates in apoptotic signaling in many types of cells and FasL can trigger Caspase cascade by cross–linking with Fas, which leads to cell death finally. Thus, the Fas/FasL system plays a crucial role in modulating apoptosis. Previous findings have shown that CD4–dependent destruction of melanocytes is partially inhibited by blocking Fas–Fas ligand interactions for autoimmune vitiligo. Functional polymorphisms of the Fas/FasL genes and Caspase genes can alter the transcriptional activities, but no published study has investigated the role of these polymorphisms in the etiology of vitiligo. Objective: To investigate the associations between functional polymorphisms of the genes in Fas apoptosis way and risk of vitiligo in Chinese populations.Methods: In a hospital–based, case–control study of vitiligo patients and vitiligo–free controls frequency–matched by age and sex, we genotyped functional polymorphisms of Fas and Caspase genes using PCR–restriction fragment length polymorphism and assessed their respective associations with vitiligo risk.Results:We found a statistically significantly increased risk of vitiligo associated with the Fas–1377G>A polymorphism (P=0.015), but no evident risk was associated with the Fas–670G >A genotypes.The two Fas polymorphisms were in linkage disequilibrium (D′=0.784, P<0.001). The Fas–AA haplotype frequency was significantly different between cases and controls (6.5% versus 2.4%, respectively; P<0.001), and the AA haplotype were associated with a significantly higher vitiligo risk (adjusted OR=3.29, 95% CI=2.05–5.29).In the combined analysis of the two variant alleles of Fas, the genotypes with 3–4 variant (risk) alleles (–1377A and–670A) were associated with an increased risk of vitiligo compared to those having 0–2 variants (adjusted OR=2.87; 95% CI=1.90–4.32). Person who carried the–1377(AG+AA)/–670(AG+AA) genotype had a higher vitiligo risk (OR=1.44; 95% CI=1.15–1.79).The combined variant (risk) genotypes of Fas–1377 gene were associated with a significantly higher risk of vitiligo, which was more pronounced among vitiligo patients of female, non-segmental group, onset age≤20 years and without family history.The serum sFas level in patients (2.03±1.23ng/ml) was significantly higher than that in controls (1.26±0.66ng/ml) (P<0.05). However, levels of each groups were similar in spite of different Fas-1377 genotypes.CASP8-652 and CASP10I522L were in highly linkage disequilibrium(D'=0.934, P<0.001). But no any statistically significant results was found about them.Conclusions: Genetic variants in the Fas gene may alter risk of vitiligo in Chinese populations. Larger studies are needed to verify these findings.