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.
Methods and 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.
Conclusion: The reported genotype in PSMA6 appears not to contribute appreciably to MI, but may contribute slightly to atherosclerosis in the present study population.