Caucasian-specific allele in non-synonymous single nucleotide polymorphisms of the gene encoding deoxyribonuclease I-like 3, potentially relevant to autoimmunity, produces an inactive enzyme

Deoxyribonuclease I-like 3 (DNase Il3), a member of human DNase I family, is postulated to be involved in the genesis of autoimmune diseases. In the DNase Il3 gene, 2 non-synonymous SNPs, R178H and R206C, have been identified, however relevant population data are not available. Genotyping of the SNP...

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Bibliographic Details
Published in:Clinica chimica acta 2009-09, Vol.407 (1), p.20-24
Main Authors: Ueki, Misuzu, Takeshita, Haruo, Fujihara, Junko, Iida, Reiko, Yuasa, Isao, Kato, Hideaki, Panduro, Arturo, Nakajima, Tamiko, Kominato, Yoshihiko, Yasuda, Toshihiro
Format: Article
Language:English
Subjects:
African Continental Ancestry Group - genetics
Alleles
Amino Acid Substitution
Animals
Asian Continental Ancestry Group - genetics
Autoimmunity - genetics
Cercopithecus aethiops
COS Cells
Deoxyribonuclease I-like 3 (DNase Il3)
Endodeoxyribonucleases - genetics
Endodeoxyribonucleases - metabolism
Ethnic variation
European Continental Ancestry Group - genetics
Female
Genotype
Genotyping
Humans
Polymorphism, Single Nucleotide
SNP
Systemic lupus erythematosus
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Summary:Deoxyribonuclease I-like 3 (DNase Il3), a member of human DNase I family, is postulated to be involved in the genesis of autoimmune diseases. In the DNase Il3 gene, 2 non-synonymous SNPs, R178H and R206C, have been identified, however relevant population data are not available. Genotyping of the SNPs was performed in healthy subjects belonging to 3 ethnic groups ( n = 1708), including nine different populations, using an amplification refractory mutation system and the PCR-RFLP technique. All of the 9 populations were typed as a single genotype in R178H. All Asian and African populations exhibited only a homozygous C686 allele in R206C, whereas a heterozygote, C686/T686, was found (frequency of 3.5–15.4%) in three Caucasian populations (Turk, German and Mexican); Caucasian-specific allele T686 was identified. The substitution of Arg by Cys corresponding to R206C resulted in elimination of DNase Il3 activity. A Caucasian-specific allele in SNP R206C produces an inactive form of DNase Il3. It seems plausible that levels of DNase Il3 activity in Caucasian subjects with the heterozygote in R206C are lower than those in individuals with the predominant homozygote. Our results may have clinical implications in relation to the prevalence of autoimmune diseases.
ISSN:0009-8981
1873-3492
DOI:10.1016/j.cca.2009.06.022