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
| Autor: | Stephen Kaptoge, Kishwar Kumar, Muhammad Azhar, Abdus Samad, Shajjia Razi Haider, Adam S. Butterworth, Nadeem Qamar, Syed Saadat Ali, Moazzam Zaidi, Zia Yaqoob, Shahzad Majeed Bhatti, Nabi Shah, Maria Samuel, Asim Saleem, Emma Gray, Simon C. Potter, Shahid Abbas, Usman Ahmad, Faisal Shahid, Muhammad Ali Memon, David Wormser, Nicole Soranzo, Zehra Memon, Hannah Blackburn, Fatima Memon, Waleed T. Kayani, Myriam Alexander, Muhammed Murtaza, Abdul Hakeem, Assadullah Kundi, Khan Shah Zaman, Junaid Zafar, Nadeem Hayat Mallick, Muhammad Ishaq, Azhar Faruqui, Nasir Sheikh, Suzannah Bumpstead, Naomi Hammond, Philippe M. Frossard, Fazal-ur-Rehman Memon, Panos Deloukas, Liaquat Ali Cheema, Kishore Kumar, Mustafa Hussain, Danish Saleheen, Ali Raza Gardezi, Asif Rasheed, Aftab Alam Gul, Emanuele Di Angelantonio, Rashid Jooma, Syed Zahed Rasheed, Abdul Ghaffar, Muhammad Fahim, John Danesh, Philip Haycock, Ahmedyar Janjua, Nazir Ahmed Memon, Jawaid Hassan Niazi, Muhammad Salman Daood |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Linkage disequilibrium Myocardial Infarction Locus (genetics) Single-nucleotide polymorphism Polymorphism Single Nucleotide Risk Assessment Linkage Disequilibrium White People Asian People Gene Frequency Risk Factors Odds Ratio Medicine Humans Genetic Predisposition to Disease Pakistan Allele business.industry Case-control study Odds ratio Middle Aged Minor allele frequency Europe Logistic Models Phenotype Meta-analysis Case-Control Studies Female Cardiology and Cardiovascular Medicine business Chromosomes Human Pair 9 Demography |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 30(7) |
| ISSN: | 1524-4636 |
| Popis: | 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 −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 =2×10 −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 =1×10 −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. Conclusion— 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. |
| Databáze: | OpenAIRE |
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