白癜风患者黑素刺激素受体1单核苷酸多态性分析

Single nucleotide polymorphisms in melanocortin-1 receptor genes in patients with vitiligo

目的检测白癜风患者黑素刺激素受体1(MC1R)基因编码区的单核苷酸多态性(SNP),探讨其在白癜风发病中的作用。方法选取40例寻常型白癜风患者作为白癜风组,38例健康体检者为对照组,另取NCBI数据库最新公布的亚洲人群(包括85例正常亚洲人)MC1R的单核苷酸多态性数据作为文献组。提取白癜风组和对照组血细胞基因组,PCR扩增MC1R基因,用直接测序法检测PCR产物。采用χ2检验分析比较三组间MC1R基因SNP的发生、分布及频率差异。结果白癜风组和对照组MC1R基因共发现5个SNP位点,分别为G274A(Val92Met)、T359C(His120His)、G488A(Gln163Arg)、C491A(Ala164Gln)、A942G(Thr312Thr),其中多态性较高的两个位点是G274A(Val92Met)和G488A(Gln163Arg);白癜风组Val92Met位点和Gln163Arg位点的多态性频率分别为26.25%和81.25%,对照组分别为22.37%和57.89%。Gln163Arg多态性在白癜风组与对照组间有显著差异(χ2=9.966,P<0.01),在白癜风组与文献组之间亦有显著差异(χ2=6.214,P<0.05),而对照组与文献组间均无显著差异(P>0.05)。Val92Met位点多态性在三组间无显著性差异(P>0.05)。新发现了一个变异位点C491A(Ala164Gln)。结论Gln163Arg的多态性可能与白癜风发病有关,Val92Met与白癜风发病无明显相关性。

Objective To detect the single nucleotide polymorphisms （SNPs） of coding region of melanocortin-1 receptor （MC1R） genes in order to evaluate the role of SNPs in etiology of vitiligo. Methods Forty patients with vitiligo vulgaris were recruited as disease group, 38 subjects for health check-up were recruited as control group, and the latest SNP data of 85 Asian MC1R listed in the National Center for Biotechnology Information（NCBI）were collected as literature group. All the genomic DNA of the subjects in both disease and control group was extracted from the blood cells. Then the MC1R gene of genomic DNA was amplified by PCR and directly sequenced. χ2 analysis was used to assess the frequencies of SNP of MC1R among the disease group, control group and literature group. Results In disease group and control group, 5 MC1R coding region SNPs were found： G274A （Val92Met）, T359C （His120His）, G488A （Gln163Arg）, C491A （Ala164Gln） and A942G （Thr312Thr）. Among them, G274A （Val92Met） and G488A （Gln163Arg） were with much higher frequencies. The frequency of G274A （Val92Met） was 26.25% in patient group and 22.37% in control group, and that of G488A （Gln163Arg） was 81.25% in patient group and 57.89% in control group. Significant difference was found in the frequency of Gln163Arg between disease group and control group（χ2=9.966, P0.01）, and it was also true between disease group and literature group（χ2=6.214, P0.05）. No significant difference existed between literature group and control group （P0.05）. And no significant difference in frequencies of the allele G274A （Val92Met） existed among the three groups （P0.05）. A novel variant allele, C491A （Ala164Gln）, was found. Conclusion Association exists between the polymorphism of Gln163Arg and pathogenesis of vitiligo, whereas no correlation exists between Val92Met and pathogenesis of vitiligo.