| Introduction:Vitiligo is a common chronic depigmented skin disorder which caused by regional melanocytes depletion. The mechanism of vitiligo is still not completely known, though there are some theories about its pathogenesis. Recently, vitiligo is thought to be a polygenic hereditary disease, which is correlated with heredity and environment.Single nucleotide polymorphism (SNP) is an important factor for deciding the susceptivity of human diseases (especially multigenic diseases).It can be a good method, especially satisfies the demand of high precision for disease related gene positioning study of hereditary disorders.Now, vitiligo is considered as one of the polygenic hereditary diseases. So screening vitiligo predisposing genes may play an important role in reveal the etiology of vitiligo. A series of potential genes are predicted to have susceptivity with vitiligo, preliminary screening of predisposing genes by application of SNP get to first base for further seeking and locating the close related genes of vitiligo. Some researchers have found vitiligo is associated with certain gene mutation or expression. These findings consist of the important genes of melanin biosynthesis, the genes of oxidative tensions and the genes related to autoimmune accommodation. We have choosed four SNPs in three genes and analysed their association with the risk of vitiligo by using PCR-RFLP method. These three genes may be associated with vitiligo, and they are also correlated to each other. We tried to identify their association with vitiligo in this study.Objective : To study the association of AA-NAT (serotonin N-acetyltransferase, AA-NAT , rate-limiting enzyme of MLT) gene exon 4 619 G/A polymorphism, IL-6 (interleukin-6,IL-6) gene promoter region -634 C/G polymorphism and ER-αgene intron 1 Pvu II T/C and Xba I A/G polymorphisms with vitiligo.Methods:The genomic DNA were extracted after we collected the clinical data and blood samples of 749 vitiligo patients and 763 normal controls of Chinese people . Then PCR-RFLP was used to study AA-NAT gene exon 4 619 G/A polymorphism, IL-6 gene promoter region -634 C/G polymorphism, ER-αgene intron 1 Pvu II T/C and Xba I A/G polymorphisms, genotypes were determined and compared.Results:AA-NAT gene exon 4 619 G/A genotype and allele frequency distributions were not significantly different between patients and controls (P>0.05). IL-6 gene promoter region -634 C/G genotype(P = 0.02)and allele(P = 0.01, OR:1.24, 95% CI:1.05–1.46)frequency distributions were significantly different between patients and controls, but were not significantly different among vitiligo patients with different stage (stable/active) , with different subtypes, with/without other autoimmune diseases and family history (P>0.05).ER-αgene intron 1 Pvu II C/T genotype distribution (P=0.001) were significantly different between patients and controls, and C allele in Pvu II was significantly more prevalent in vitiligo patients than in the controls (P=0.002, OR:1.27, 95% CI:1.09–1.47).Intron 1 Pvu II C/T genotype distribution (P = 0.03) and C allele frequency (P = 0.02, OR:1.29, 95% CI:1.04–1.58) were significantly different between female vitiligo patients and female controls. C/T genotype distribution (P = 0.04) and C allele frequency (P = 0.03, OR:1.25, 95% CI:1.02–1.52) were also showed difference between male vitiligo patients and male controls. The genotype and allele frequency distributions were not significantly different among the segmental and the other three common type of vitiligo patients, except segmental vs universal is significantly different in genotype frequency distribution (P=0.04). P value was lower than 0.05 when the C/T genotype frequency (P=0.04) was compared between onset age of lower than 10 (≤10)and 11-20 years old; P value was near 0.05 in comparisons of genotype (P=0.08) between the male and the female patients.The rest are no stastic differences among vitiligo patients with different stage (stable/active),with/without other autoimmune diseases and family history (P>0.05).ER-αgene in intron 1 XbaI A/G polymorphism genotype distributions and allele frequencies were not significantly different between patients and controls. And the results were also not significantly different among vitiligo patients with different subtypes, with/without other autoimmune diseases (P>0.05).Allele and genotype frequencies of the ER-αgene intron 1 Pvu II C/T and XbaI A/G haplotypes compared among the cases and controls, TA is a protect factor while CA carrier is easy to commit vitiligo, and the results shows the more mutation haplotype genotypes, the more associations with risk of vitiligo(P=0.001, OR:1.53, 95% CI:1.12-2.10).Conclusions:We conclude that 619 G/A polymorphism in AA-NAT gene exon 4 and XbaI A/G polymorphism in ER-αgene intron 1 are not associated with the risk of vitiligo. -634 C/G in IL-6 gene promoter region is associated with the risk of vitiligo, C allele is a protect factor while G allele carrier is easy to commit vitiligo. Pvu II T/C polymorphism in ER-αintron 1 is also associated with vitiligo, women and onset age lower than 10 with C allele were more easily subject to vitiligo among vitiligo patients. ER-αgene Pvu II and Xba I polymorphisms haplotypes were analyzed among the cases and controls showed that ER-αgene may be a possible risk factor for vitiligo patients.
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