Department of Legal Medicine, Shimane University School of Medicine, Izumo, Shimane, Japan.
Electrophoresis. 2012 Sep;33(18):2852-8. doi: 10.1002/elps.201200260.
Five SNPs in the human DNase II gene have been reported to be associated with rheumatoid arthritis (RA). Genotype and haplotype analysis of 14 SNPs, nine SNPs of which reported in the NCBI dbSNP database in addition to these five SNPs, was performed in healthy subjects. The enzymatic activities of the amino acid substituted DNase II corresponding to each SNP and serum DNase II in healthy Japanese, and promoter activities derived from each haplotype of the RA-related SNPs were measured. Significant correlations between genotype in each RA-related SNP and enzymatic activity levels were found; alleles associated with RA exhibited a reduction in serum DNase II activity. Furthermore, the promoter activities of each reporter construct corresponding to predominant haplotypes in three SNPs in the promoter region of the gene exhibited significant correlation with levels of serum DNase II activity. These findings indicate these three SNPs could alter the promoter activity of DNASE2, leading to a decline in DNase II activity in the serum through gene expression. Since the three SNPs in the promoter region of the DNase II gene could affect in vivo DNase II activity through reduction of the promoter activity, it is feasible to identify these SNPs susceptible to RA.
已有五项人类 DNA 酶 II 基因的单核苷酸多态性（SNP）被报道与类风湿关节炎（RA）相关联。在健康人群中，对 14 项 SNP 进行了基因分型和单体型分析，其中 9 项 SNP 是在 NCBI dbSNP 数据库中报道的，除了这 5 项 SNP 之外。对每个 SNP 对应的氨基酸取代 DNA 酶 II 的酶活性以及健康日本人的血清 DNA 酶 II 进行了测量。在每个与 RA 相关的 SNP 的基因型与酶活性水平之间发现了显著的相关性；与 RA 相关的等位基因表现出血清 DNA 酶 II 活性降低。此外，基因启动子区域中三个 SNP 的主要单体型对应的每个报告基因构建体的启动子活性与血清 DNA 酶 II 活性水平呈显著相关性。这些发现表明，这三个 SNP 可以改变 DNASE2 的启动子活性，从而通过基因表达导致血清中 DNA 酶 II 活性下降。由于 DNA 酶 II 基因启动子区的三个 SNP 可以通过降低启动子活性来影响体内 DNA 酶 II 活性，因此可以识别这些易患 RA 的 SNP。
