Validation of the association between the gene encoding proteasome subunit alpha type 6 and myocardial infarction in a Japanese population.
BACKGROUND
Recently, a large case-control study (2,851 cases and 2,592 controls) reported that a functional single nuclear polymorphism (SNP) in the proteasome subunit alpha type 6 gene (PSMA6) conferred a risk of myocardial infarction (MI) in a Japanese population. The SNP (exon 1, -8C/G) is located in the 5' untranslated region of exon 1, and the risk-conferring allele G appears to enhance the transcription of PSMA6, which may exaggerate inflammation through activation of nuclear factor-kappa beta protein. The frequency of the risk conferring genotype (GG) in cases was reported to be greater than that in controls (12.4% vs 8.9%). The purpose of the present study was to validate this observation in our study population.


RESULTS
Subjects with MI (n=433) were recruited from the outpatient clinic of the National Cardiovascular Center. Control subjects (n=2,186) were recruited from the Suita study. The frequencies of the GG genotype did not significantly differ between the control (9.8%) and MI groups (10.6%). Moreover, this genotype was not associated with C reactive protein levels in the Suita study. However, the GG genotype was significantly associated with greater intima-media thickness (n=2,051, p=0.015) after adjusting for blood pressure, sex, body mass index and age in the Suita study.


CONCLUSIONS
The reported genotype in PSMA6 appears not to contribute appreciably to MI, but may contribute slightly to atherosclerosis in the present study population.
Takashima
Naoyuki
N
Department of Epidemiology, National Cardiovascular Center, Suita. ntaka@ri.ncvc.go.jp
Shioji
Keisuke
K
Kokubo
Yoshihiro
Y
Okayama
Akira
A
Goto
Yoichi
Y
Nonogi
Hiroshi
H
Iwai
Naoharu
N
D000368:Aged; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics* / Q000502:physiology; D009203:Myocardial Infarction / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology
D009097:Multienzyme Complexes; D002097:C-Reactive Protein; C465641:PSMA6 protein, human; D046988:Proteasome Endopeptidase Complex