| Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans. | |
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MedLine Citation:
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PMID: 20395598 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. METHODS AND RESULTS: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis. CONCLUSIONS: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies. |
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Authors:
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Danish Saleheen; Myriam Alexander; Asif Rasheed; David Wormser; Nicole Soranzo; Naomi Hammond; Adam Butterworth; Moazzam Zaidi; Philip Haycock; Suzannah Bumpstead; Simon Potter; Hannah Blackburn; Emma Gray; Emanuele Di Angelantonio; Stephen Kaptoge; Nabi Shah; Maria Samuel; Ahmedyar Janjua; Nasir Sheikh; Shajjia Razi Haider; Muhammed Murtaza; Usman Ahmad; Abdul Hakeem; Muhammad Ali Memon; Nadeem Hayat Mallick; Muhammad Azhar; Abdus Samad; Syed Zahed Rasheed; Ali Raza Gardezi; Nazir Ahmed Memon; Abdul Ghaffar; Fazal-ur-Rehman Memon; Khan Shah Zaman; Assadullah Kundi; Zia Yaqoob; Liaquat Ali Cheema; Nadeem Qamar; Azhar Faruqui; Rashid Jooma; Jawaid Hassan Niazi; Mustafa Hussain; Kishore Kumar; Asim Saleem; Kishwar Kumar; Muhammad Salman Daood; Fatima Memon; Aftab Alam Gul; Shahid Abbas; Junaid Zafar; Faisal Shahid; Zehra Memon; Shahzad Majeed Bhatti; Waleed Kayani; Syed Saadat Ali; Muhammad Fahim; Muhammad Ishaq; Philippe Frossard; Panos Deloukas; John Danesh |
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Publication Detail:
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Type: Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Review Date: 2010-04-15 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-17 Completed Date: 2010-07-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1467-73 Citation Subset: IM |
Affiliation:
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Center for Non-Communicable Diseases, Karachi, Pakistan. danish.saleheen@cncdpk.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Asian Continental Ancestry Group
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genetics* Case-Control Studies Chromosomes, Human, Pair 9* Europe European Continental Ancestry Group / genetics* Female Gene Frequency Genetic Predisposition to Disease Humans Linkage Disequilibrium Logistic Models Male Middle Aged Myocardial Infarction / ethnology, genetics* Odds Ratio Pakistan Phenotype Polymorphism, Single Nucleotide* Risk Assessment Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
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//British Heart Foundation; //Medical Research Council; //Wellcome Trust |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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