Genetic and expression analysis of SNP s in the human deoxyribonuclease II: SNP s in the promoter region reduce its in vivo activity through decreased promoter activity

• Published in: Electrophoresis 2012-09, Vol.33 (18), p.2852-2858
• Main Authors: Kimura‐Kataoka, Kaori, Yasuda, Toshihiro, Fujihara, Junko, Toga, Tomoko, Ono, Rei‐Ichiro, Otsuka, Yosuke, Ueki, Misuzu, Iida, Reiko, Sano, Rie, Nakajima, Tamiko, Kominato, Yoshihiko, Kato, Hideaki, Takeshita, Haruo
• Format: Article
• Language: English
• ISSN: 0173-0835; 1522-2683
• DOI: 10.1002/elps.201200260

Five SNP s in the human DN ase II gene have been reported to be associated with rheumatoid arthritis ( RA ). Genotype and haplotype analysis of 14 SNP s, nine SNPs of which reported in the NCBI db SNP database in addition to these five SNP s, was performed in healthy subjects. The enzymatic activities of the amino acid substituted DN ase II corresponding to each SNP and serum DN ase II in healthy Japanese, and promoter activities derived from each haplotype of the RA ‐related SNP s 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 DN ase II activity. Furthermore, the promoter activities of each reporter construct corresponding to predominant haplotypes in three SNP s in the promoter region of the gene exhibited significant correlation with levels of serum DN ase II activity. These findings indicate these three SNP s could alter the promoter activity of DNASE 2 , leading to a decline in DN ase II activity in the serum through gene expression. Since the three SNP s in the promoter region of the DN ase II gene could affect in vivo DN ase II activity through reduction of the promoter activity, it is feasible to identify these SNP s susceptible to RA .