| Introduction: Vitiligo is a common skin disease characterized by the development of white macules and patches associated with local melanocytes loss. The pathomechanism of vitiligo has still not been completely clarified, various possible pathomechanisms have been proposed, including the immune-mediated, the auto-cytotoxic/metabolic, the genetic factors and the neural dysfunction. But none of them can explain the pathomechanism of vitiligo perfectly. Much clinical evidence and experimental data suggests that vitiligo is an autoimmune disease with polygenic inheritance and suspect genes play an important role.Catechol-O-methyltransferase (COMT) is an enzyme that catalyses the O-methylation of biologically active or toxic catechols and plays an important role in the metabolism of drugs and neurotransmitters. A common single nucleotide polymorphism (SNP) in codon 158 of the COMT gene codes for a substitution of valine (Val) by methionine (met), resulting in reduced thermostability and activity of the enzyme. In melanocytes, this SNP may change the activity of the enzyme, induce high level of toxic o-quinones and destroy the melanocytes.The PTPN22 gene product LYP is an important down regulator of T lymphocyte activiation. An increase in PTPN22 activity would increase the threshold required for effective TCR signaling in developing thymocytes, resulting in a lack of negative selection of autoreactive T cells. Treg cells are a major regulatory mechanism to prevent the emergence of antoimmunity, inceased PTPN22 activity could lead to reduced TCR signaling, thus, reduced Treg function. Either or both of these two mechanisms could lead to a state of susceptibility for autoimmune disorders, such as vitiligo.Objective: We hypothesized the COMT-158 G>A polymorphism and PTPN22 gene SNPs were associated with the risk of vitiligo in Han Chinese people.Methods: In a hospital-based case-control study of 749 patients with vitiligo and 763 vitiligo-free controls was made in frequency according to the age and sex. COMT-158 G>A polymorphism and PTPN22 gene promoter region -1123 polymorphism were genotyped by using the PCR sequence specific primer (PCR-SSP) technique. PTPN22+1858 polymorphism and 3'UTR SNP rs3811021 were were genotyped by using the PCR -RFLP technique. Results: We found that an increased risk of vitiligo was associated with the COMT-158GA (adjusted odds ratio [OR], 1.39; 95% CI, 1.13-1.72) and -158AA (adjusted OR, 1.55; 95% CI, 0.99-2.42) genotypes, compared with the -158GG genotype. Consistently we found that a high risk of vitiligo was associated with the COMT-158 combined genotype GA+AA (adjusted OR, 1.41; 95% CI, 1.15-1.74), compared with the -158GG genotype, especially in the early onset (adjusted OR=1.95, 95% CI=1.45-2.60) and female (adjusted OR=1.74, 95% CI=1.29-2.36)., from the clinical types analysis we found that this high risk association was observed in the subjects with vulgaris vitiligo (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 found in patients with acrofacial vitiligo (adjusted OR=1.53, 95% CI=0.86-2.73) and segment vitiligo (adjusted OR=1.35, 95% CI=0.72-2.51) .We didn't find PTPN22 +1858 polymorphism in all the case and control subjects by two different PCR-RFLP techniques. The frequence of PTPN22-1123 C allele is significant high in the cases compared with control subjects(44.1% vs. 40.0%, P = 0.025).We found that an increased risk of vitiligo was associated with the PTPN22-1123 CC (adjusted odds ratio [OR], 1.29; 95% CI, 1.00-1.68) compared with the PTPN22-1123 GG +CG combined genotype. We didn't find significant different distribution of rs 3811021 C allele among the case and control subjects(20.6% vs. 20.8%, P = 0.928). Furthermore, in the haplotype analysis of PTPN22 gene, we found that the PTPN22 haplotype genotypes with 2-4 variant (risk) alleles were associateh with an increased risk of vitiligo compared to 0-1 vatiants. We also found PTPN22 haplotype genotypes with 2-4 variant (risk) alleles were associateh with an increased risk of vitiligo in male and <20 age groups. In the non-segment vitiligo subjects the PTPN22 haplotype genotypes with 2-4 variant (risk) alleles was significant high compared with control subjects.In conclusion: As far as we know, this is the first study about the association between the COMT-158 polymorphism, the PTPN22 polymorphisms and the haplotypes genotypes and the vitiligo in the Han Chinese population. Larger, population-based studies are needed to confirm these findings. |
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