The exon 1–8C/G SNP in the PSMA6 gene contributes only a small amount to the burden of myocardial infarction in 6946 cases and 2720 controls from a United Kingdom population

Abstract

The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Polymorphisms in the gene encoding subunit a type 6 (PSMA6) -in particular the rs1048990 exon 1-8C/G SNP -have been implicated with susceptibility to myocardial infarction (MI) in a Japanese study. We examined whether several polymorphisms in the PSMA6 gene were related to MI risk in 6946 nonfatal MI cases and 2720 unrelated controls in a UK population. The homozygous GG genotype for rs1048990 was much less frequent in this UK population than in the Japanese population (2.1 vs 8.9%), and was associated with an odds ratio (OR) for MI of 1.09 (95% confidence interval (CI): 0.98 -1.21) per G allele in a co-dominant genetic model and 1.32 (95% CI: 0.90-1.93) in a recessive genetic model. Although not statistically significant, these results for this variant are still consistent with the Japanese hypothesisgenerating study. Our findings, when taken together with four other studies (including the hypothesisgenerating one), yielded a combined OR for MI of 1.15 (95% CI: 1.08 -1.21) per G allele in a co-dominant model and 1.38 (95% CI: 1.22 -1.57) for the GG genotype in a recessive model. Larger studies involving more than 10 000 disease cases would be required to further elucidate the role of this variant for susceptibility to MI. However, given the rarity of this variant in Caucasians, the attributable risk of rs1048990 for MI is unlikely to be great in western populations.

Replication studies for the association of PSMA6 polymorphism with coronary artery disease in East Asian populations

“…So far there are six other replication studies including that by Ozaki et al, 7 and five of them except for Ozaki's replication study failed to replicate the significant association of PSMA6 À8C4G with CAD. [11][12][13][14][15] Therefore, we performed a meta-analysis of the data obtained in this study for the Japanese and Korean populations and the data in the previous replication studies. As shown in Figure 1, the association was found to be modest with a statistical significance (OR¼1.08, 95% CI; 1.02-1.14, P¼0.0057).…”

Haplotypes Encompassing the KIAA0391 and PSMA6 Gene Cluster Confer a Genetic Link for Myocardial Infarction and Coronary Artery Disease

“…Not surprisingly therefore, the proteasomal alpha subunit type 6 gene ( PSMA6 ), a component of the ubiquitin‐proteasome system has been associated with MI (Ozaki et al, 2006; Barbieri et al, 2008), type 2 diabetes mellitus (DM2) (Sjakste et al, 2007b), greater intima‐media thickness (Takashima et al, 2007), and possibly atherosclerosis (Takashima et al, 2007). On the other hand, its role in conferring risk for cardiovascular‐related events in general has been called into question recently by a number of studies pointing to lack of association with these disorders in some ethnic groups (Sjakste et al, 2007b; Takashima et al, 2007; Banerjee et al, 2008; Bennett et al, 2008).…”

Genetic variants associated with myocardial infarction in the PSMA6 gene and Chr9p21 are also associated with ischaemic stroke

“…We selected 20 SNPs that have been shown to be associated with either CAD or MI for analysis in this study [20][21][22][23][24][25][26][27][28][29]. All SNPs were selected based on findings from prior genome-wide association studies (GWASs) with the exception of rs1048990 in PSMA6, which was selected because of several independent replications in different populations.…”