Seven nonsynonymous SNP s in the gene encoding human deoxyribonuclease II may serve as a functional SNP potentially implicated in autoimmune dysfunction

Many nonsynonymous SNP s in the human DN ase II gene ( DNASE2 ), potentially relevant to autoimmunity in conditions such as rheumatoid arthritis, have been identified, but only limited population data are available and no studies have evaluated whether such SNP s are functional. Genotyping of all the 15 nonsynonymous human DN ase II SNP s was performed in three ethnic groups including 16 different populations using the PCR ‐restriction fragment length polymorphism technique. A series of constructs corresponding to each SNP was examined. Fifteen nonsynonymous SNP s in the gene, except for p.Val206Ile in a K orean population, exhibited a mono‐allelic distribution in all of the populations. On the basis of alterations in the activity levels resulting from the corresponding amino acid substitutions, four activity‐abolishing and five activity‐reducing SNP s were confirmed to be functional. The amino acid residues in activity‐abolishing SNP s were conserved in animal DN ase II. All the nonsynonymous SNP s that affected the catalytic activity of human DN ase II showed extremely low genetic heterogeneity. However, a minor allele of seven SNP s producing a loss‐of‐function or extremely low activity‐harboring variant could serve as a genetic risk factor for autoimmune dysfunction. These functional SNP s in DNASE 2 may have clinical implications in relation to the prevalence of autoimmune diseases.