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Quantitative assessment of the influence of PSMA6 variant (rs1048990) on coronary artery disease risk

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Abstract

The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Recently, an association of a functional sequence variation, -8C/G, in the human proteasome subunit a type 6 gene (PSMA6) with the susceptibility to coronary artery disease (CAD) was reported. After that, several validation studies have been conducted among various ethnic populations, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis of 15,991 cases and 16,784 controls from 10 case–control studies was performed. Potential sources of heterogeneity including ethnicity, sample size and HWE status of study were also assessed. In a combined analysis, the summary per-allele OR for CAD of the -8C/G polymorphism was 1.09 (95 % CI: 1.02–1.16; P = 0.006). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians for the polymorphism; while no significant associations were found among Caucasians and other ethnic population in all genetic models. When restricted to studies concerning myocardial infarction patients, significant associations were detected in all genetic models. Furthermore, significant difference of PSMA6 mRNA expression was found between genotypes. In conclusion, this meta-analysis suggests that G allele of PSMA6-8C/G polymorphism is a risk factor associated with increased CAD susceptibility, but these associations vary in different ethnic populations.

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Abbreviations

CAD:

Coronary artery disease

MI:

Myocardial infarction

PSMA6:

Proteasome subunit α type 6

CI:

Confidence interval

HWE:

Hardy–Weinberg equilibrium

OR:

Odds ratio

References

  1. Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M (2002) Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 347:1916–1923

    Article  PubMed  CAS  Google Scholar 

  2. Broeckel U, Hengstenberg C, Mayer B et al (2002) A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 30:210–214

    Article  PubMed  CAS  Google Scholar 

  3. Topol EJ, Smith J, Plow EF, Wang QK (2006) Genetic susceptibility to myocardial infarction and coronary artery disease. Hum Mol Genet 15:R117–R123

    Article  PubMed  CAS  Google Scholar 

  4. Libby P (2002) Atherosclerosis in inflammation. Nature 420:868–874

    Article  PubMed  CAS  Google Scholar 

  5. Herrmann J, Ciechanover A, Lerman LO, Lerman A (2004) The ubiquitin–proteasome system in cardiovascular diseases-a hypothesis extended. Cardiovasc Res 61:11–21

    Article  PubMed  CAS  Google Scholar 

  6. Meiners S, Laule M, Rother W et al (2002) Ubiquitin–proteasome pathway as a new target for the prevention of restenosis. Circulation 105:483–489

    Article  PubMed  CAS  Google Scholar 

  7. Elliott PJ, Zollner TM, Boehncke WH (2003) Proteasome inhibition: a new anti-inflammatory strategy. J Mol Med 8:235–245

    Google Scholar 

  8. Ozaki K, Sato H, Iida A et al (2006) A functional SNP in PSMA6 confers risk of myocardial infarction in the Japanese population. Nat Genet 38:921–925

    Article  PubMed  CAS  Google Scholar 

  9. Holm K, Melum E, Franke A, Karlsen TH (2010) SNPexp—a web tool for calculating and visualizing correlation between HapMap genotypes and gene expression levels. BMC Bioinformatics 11:600

    Article  PubMed  Google Scholar 

  10. International HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796

    Article  Google Scholar 

  11. Stranger BE, Forrest MS, Dunning M et al (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315:848–853

    Article  PubMed  CAS  Google Scholar 

  12. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  14. Woolf B (1955) On estimating the relation between blood group and disease. Ann Hum Genet 19:251–253

    Article  PubMed  CAS  Google Scholar 

  15. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  16. Sjakste T, Poudziunas I, Ninio E et al (2007) SNPs of PSMA6 gene–investigation of possible association with myocardial infarction and type 2 diabetes mellitus. Genetika 43:553–559

    PubMed  CAS  Google Scholar 

  17. Takashima N, Shioji K, Kokubo Y, Okayama A, Goto Y, Nonogi H, Iwai N (2007) Validation of the association between the gene encoding proteasome subunit alpha type 6 and myocardial infarction in a Japanese population. Circ J 71:495–498

    Article  PubMed  CAS  Google Scholar 

  18. Bennett DA, Xu P, Clarke R, Zondervan K, Parish S, Palmer A, Cardon L, Peto R, Lathrop M, Collins R (2008) The exon 1-8C/G SNP in the PSMA6 gene contributes only a small amount to the burden of myocardial infarction in 6,946 cases and 2,720 controls from a United Kingdom population. Eur J Hum Genet 16:480–486

    Article  PubMed  CAS  Google Scholar 

  19. Barbieri M, Marfella R, Rizzo MR, Boccardi V, Siniscalchi M, Schiattarella C, Siciliano S, Lemme P, Paolisso G (2008) The −8 UTR C/G polymorphism of PSMA6 gene is associated with susceptibility to myocardial infarction in type 2 diabetic patients. Atherosclerosis 201:117–123

    Article  PubMed  CAS  Google Scholar 

  20. Liu X, Wang X, Shen Y, Wu L, Ruan X, Lindpaintner K, Yusuf S, Engert JC, Anand S, Tan X, Liu L (2009) The functional variant rs1048990 in PSMA6 is associated with susceptibility to myocardial infarction in a Chinese population. Atherosclerosis 206:199–203

    Article  PubMed  CAS  Google Scholar 

  21. Banerjee I, Pandey U, Hasan OM, Parihar R, Tripathi V, Ganesh S (2009) Association between inflammatory gene polymorphisms and coronary artery disease in an Indian population. J Thromb Thrombolysis 27:88–94

    Article  PubMed  CAS  Google Scholar 

  22. Alsmadi O, Muiya P, Khalak H, Al-Saud H, Meyer BF, Al-Mohanna F, Alshahid M, Dzimiri N (2009) Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. Ann Hum Genet 73:475–483

    Article  PubMed  CAS  Google Scholar 

  23. Hinohara K, Nakajima T, Sasaoka T, Sawabe M, Lee BS, Ban J, Park JE, Izumi T, Kimura A (2009) Replication studies for the association of PSMA6 polymorphism with coronary artery disease in East Asian populations. J Hum Genet 54:248–251

    Article  PubMed  CAS  Google Scholar 

  24. Ikeda S, Tanaka N, Arai T, Chida K, Muramatsu M, Sawabe M (2012) Polymorphisms of LTA, LGALS2, and PSMA6 genes and coronary atherosclerosis: a pathological study of 1503 consecutive autopsy cases. Atherosclerosis 221:458–460

    Article  PubMed  CAS  Google Scholar 

  25. Kozak M (1997) Recognition of AUG and Alternative Initiator Codos Is Augmented by G in Position +4 but is not Generally Affected by the Nucleotides in Position +5 and +6. EMBO J 16:2482–2492

    Article  PubMed  CAS  Google Scholar 

  26. Kozak M (2002) Pushing the limits of the scanning mechanism for initiation of translation. Gene 299:1–34

    Article  PubMed  CAS  Google Scholar 

  27. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:895–899

    Article  PubMed  CAS  Google Scholar 

  28. Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The project as supported by a leadership award to H. W (PWRd2011-04) and by the key discipline construction funding (PWZxk201005) from the Pudong New Area Health Bureau, Shanghai, China.

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Authors and Affiliations

  1. Department of Cardiology, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200135, People’s Republic of China

    Hairong Wang, Hua Zhu, Peihua Gong, Jie Lin, Jide Lu & Jianping Qiu

  2. Departments of Neurology, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200135, People’s Republic of China

    Mei Jiang

  3. Department of Cardiology, Shanghai Xuhui Central Hospital, 966 Middle Huahai Road, Shanghai, 200031, People’s Republic of China

    Qihong Chen

Authors
  1. Hairong Wang
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  2. Mei Jiang
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  3. Hua Zhu
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  4. Qihong Chen
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  5. Peihua Gong
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  6. Jie Lin
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  7. Jide Lu
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  8. Jianping Qiu
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Corresponding authors

Correspondence to Jide Lu or Jianping Qiu.

Additional information

Hairong Wang and Mei Jiang contributed equally to this study.

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Wang, H., Jiang, M., Zhu, H. et al. Quantitative assessment of the influence of PSMA6 variant (rs1048990) on coronary artery disease risk. Mol Biol Rep 40, 1035–1041 (2013). https://doi.org/10.1007/s11033-012-2146-2

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  • DOI: https://doi.org/10.1007/s11033-012-2146-2

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