Vitiligo In Chinese Population Research Articles

801 In vivo modeling of vitiligo associated ZMIZ1 gene identified by genome-wide assciation study

Previously we identified Zinc Finger MIZ-Type Containing 1 (ZMIZ1) gene as a suggest susceptibility gene associated with vitiligo in Chinese population. By conducting fine-mapping analysis, ZMIZ1 was confirmed to be a novel susceptibility gene and suggested to have functional impact on TF binding and thus influence the development of vitiligo. ZMIZ1 has previously been associated with multiple autoimmune diseases, including MS and the autoimmune diseases psoriasis, Crohn's disease, and inflammatory bowel disease. This suggests the gene has an important role in the immune response. However, the role in the pigmentation is unclear. Hereby we investigated the role of zmzi1 in zebrafish development using morpholino oligonucleotides (MO) to generate a zebrafish loss of function model. Two co-orthologs of human ZMIZ1 have been annotated in the zebrafish genome (zZMIZ1a & zZMIZ1b). We firstly studied the temporal and spatial expression of these two transcripts in the developing zebrafish embryo, which suggested that the expression of zZMIZ1a and zZMIZ1b in brain starts to emerge with ubiquitous fashion since 2dpf. After successful design and validation of RNA splicing interference effects of Moss, we observed zZmiz1a and zZmiz1b MO could cause zebrafish embryonic developmental delay and malformations. We further analysis the melanin content in the morphants at quantitative level. For zZm1z1a there is a significant reduction of melanin content with dosage dependent patter; but for zZm1z1b only at highest concentration of MO injection there is a significant reduction of melanin content. We also performed tyrosinase inhibition assay and found there is no significant difference between morphants and WT. This study successfully modeled a susceptibility gene identified by GWAS in zebrafish loss-of function model and provides insights into the biological functions of pigmentation.

A comprehensive association analysis confirms ZMIZ1 to be a susceptibility gene for vitiligo in Chinese population

BackgroundZMIZ1 has been shown to be associated with multiple autoimmune diseases and play a role in the development of melanocyte. The association of ZMIZ1 with vitiligo was also suggested, but...

Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: A genotype–phenotype correlation study

Vitiligo is an acquired depigmentation disorder, and reactive oxygen species play an important role in melanocyte damage. Base excision repair is the major pathway responsible for removing reactive oxygen species-induced DNA damage, in which APE1, ADPRT, and XRCC1 play key roles. To investigate the association between genetic variations of these genes and the risk of vitiligo in Chinese populations, we genotyped APE1-Asp148Glu, ADPRT-Val762Ala, and XRCC1-Arg399Gln polymorphisms and measured serum 8-OHdG levels in a hospital-based case–control study. We found that a significantly increased risk of vitiligo was associated with the APE1 Asp/Glu (adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02–1.52) and Glu/Glu genotypes (adjusted OR 1.48; 95% CI 1.13–1.93), compared with the APE1 Asp/Asp genotype, whereas no vitiligo risk was associated with the genotypes ADPRT-Val762Ala and XRCC1-Arg399Gln. Furthermore, serum 8-OHdG levels were elevated in the APE1-148Glu allele carriers (Asp/Glu+Glu/Glu), in an allele dose-response manner, with the risk of vitiligo (Ptrend<0.05). In addition, we found that the APE1-148Glu variant increased the 8-OHdG levels of cultured human melanocytes treated with H2O2, without any impact on the endonuclease activity. These data suggest that the APE1-Asp148Glu polymorphism aggravates oxidative stress in human melanocytes and contributes to genetic predisposition to vitiligo in Chinese people.

A functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene alter vitiligo risk in a Chinese population

Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes. The COMT-158 polymorphism can reduce COMT enzyme activity and may thus lead to the overproduction of toxic radicals in the melanocyte microenvironment. To determine whether this polymorphism in the COMT gene is associated with an increased risk of vitiligo in Chinese populations, we used a polymerase chain reaction sequence-specific primer (PCR-SSP) technique to determine the frequency of the polymorphism COMT-158 G > A in 749 vitiligo patients and 763 healthy controls. We found that compared to the COMT-158 GG genotype, the COMT-158 GA genotype (adjusted odds ratio [OR], 1.39; 95% confidence interval [CI], 1.13-1.72) and the combined GA + AA genotype (adjusted OR, 1.41; 95% CI, 1.15-1.74) were associated with an increased risk of generalized vitiligo. The association was more pronounced in patients with early-onset vitiligo (adjusted OR, 1.95; 95% CI, 1.45-2.60), those with a family history of vitiligo (adjusted OR, 3.84; 95% CI, 2.47-5.96), and female patients (adjusted OR, 1.74; 95% CI, 1.29-2.36). When we further clinically stratified the vitiligo patients according to their disease types, we found that the combined GA + AA genotype was associated with vitiligo vulgaris (adjusted OR, 1.31; 95% CI, 1.02-1.68), focal vitiligo (adjusted OR, 1.62; 95% CI, 1.17-2.25), and universal vitiligo (adjusted OR, 1.50; 95% CI, 0.98-2.30), but not with acrofacial vitiligo (adjusted OR, 1.53; 95% CI, 0.86-2.73) or segmental vitiligo (adjusted OR, 1.35; 95% CI, 0.72-2.51). In conclusion, this COMT gene polymorphism may have contributed to the etiology of vitiligo in our Chinese population. Larger population-based studies are required to verify our findings.

Functional Polymorphisms of the FAS Gene Associated with Risk of Vitiligo in Chinese Populations: A Case–Control Analysis

The FAS/FASLG system plays a key role in regulating apoptosis. Previous findings have shown that CD4-dependent destruction of melanocytes is partially inhibited by blocking FAS-FASLG interactions in autoimmune vitiligo. Functional polymorphisms of the FAS and FASLG genes can alter their transcriptional activities. In a hospital-based case-control study of 750 vitiligo patients and 756 controls, we genotyped the FAS-1377 G>A, FAS-670 A>G, and FASLG-844 T>C polymorphisms and assessed their association with the risk of vitiligo. We found that a significantly increased risk of vitiligo was associated with the FAS-1377 AA genotype (adjusted odds ratio (OR), 1.49; 95% confidence interval (CI), 1.07-2.08) and the FAS-1377 AG genotype (adjusted OR, 1.31; 95% CI, 1.05-1.63) when compared with the FAS-1377 GG genotype. However, no evident risk was associated with FAS-670 G>A genotypes. In the combined analysis of the two variant alleles of FAS, genotypes with 3 to 4 risk alleles were associated with an increased risk of vitiligo compared with those having 0-2 variants (adjusted OR, 2.87; 95% CI, 1.90-4.32). In conclusion, genetic variants in the FAS gene may affect the risk of vitiligo in Chinese populations.

Association of COX2 functional polymorphisms and the risk of vitiligo in Chinese populations

Background Cyclooxygenase-2 (COX2) plays an important role in the production of prostaglandin E2 (PGE2), which is made by epidermal keratinocytes in response to ultraviolet radiation (UVR). PGE2 is important for the proliferation and melanogenesis of epidermal melanocytes, the loss of which leads to vitiligo. COX2-1195A > G, -765G > C, and -8473T > C polymorphisms may influence the mRNA levels of COX2 and affect the production of PGE2 subsequently. Therefore, we supposed that these polymorphisms may be associated with vitiligo. Objective The aim of the study was to elucidate the association between three functional COX2 polymorphisms and the risk of vitiligo. Methods This was a hospital-based, case–control study of 755 vitiligo patients and 774 vitiligo-free controls who were frequency matched by age and sex. We genotyped COX2-1195A > G, -765G > C , and -8473T > C polymorphisms by using PCR-restriction fragment length polymorphism (RFLP) method and assessed their respective associations with the risk of vitiligo in Han Chinese populations. Results We found a statistically significant increased risk of vitiligo to be associated with the COX2-1195 G variant allele ( p = 0.004). Significantly higher vitiligo risks were found among subgroups with these characteristics: age >20 years, male, active, nonsegmental vitiligo, and onset age >20 years. In addition, the interaction between COX2-1195 and COX2- 8473 was statistically significant ( p = 0.004). Conclusion For the first time, we provide evidence that functional polymorphisms in the COX2 gene may influence the risk of vitiligo in Han Chinese populations, suggesting new clues that help to clarify the pathogenesis of vitiligo. Larger studies are needed to verify these findings.