title: Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese.
abstract: To reveal genetic risk factors of nonfamilial idiopathic cardiomyopathy (IDC) in Japanese, polymorphisms in the SOD2 and HLA-DRB1 genes were investigated in 86 patients and 380 healthy controls. There was a significant excess of homozygotes for the V allele [Val versus Ala (A allele), a polymorphism in the leader peptide of manganese superoxide dismutase at position 16] of the SOD2 gene in the patients compared with the controls (87.2% versus 74.7%, odds ratio = 2.30, p = 0.013, pc < 0.03), and a significant increase in the frequency of HLA-DRB1*1401 in the patients was confirmed (14.0% vs 4.5%, odds ratio = 3.46, p = 0.001, pc < 0.03). A two-locus analysis suggested that these two genetic markers (SOD2-VV genotype and DRB1*1401) may play a synergistic role in controlling the susceptibility to nonfamilial IDC. In addition, processing efficiency of Val-type SOD2 leader peptide in the presence of mitochondria was siginificantly lower than that of the Ala-type by 11 +/- 4%, suggesting that this lower processing efficiency was in part an underlying mechanism of the association between the SOD2-VV genotype and nonfamilial IDC.
authors.affiliation: Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 101, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hiroi
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Nishi
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: A
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D016017:Odds Ratio; D015345:Oligonucleotide Probes / Q000235:genetics; D011110:Polymorphism, Genetic; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015345:Oligonucleotide Probes; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase