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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-09-2888. This Article Full Text (PDF) All Versions of this Article: 2002-09-2888v1 101/8/3037    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Butt, C. Articles by Xie, Y.-G. Search for Related Content PubMed PubMed Citation Articles by Butt, C. Articles by Xie, Y.-G. Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted September 20, 2002 Accepted December 5, 2002 COMBINED CARRIER STATUS OF PROTHROMBIN 20210A AND FACTOR XIII-A L34 ALLELES AS A STRONG RISK FACTOR FOR MYOCARDIAL INFARCTION: EVIDENCE OF A GENE-GENE INTERACTION Christopher Butt, Hong Zheng, Edward Randell, Desmond Robb, Patrick Parfrey, and Ya-Gang Xie* Laboratory Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada Laboratory Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada Laboratory Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; Pediatrics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada * Corresponding author; email: yxie{at}mun.ca. Studies associating the prothrombin 20210A (FII 20210A), Factor V Leiden (FVL), and Factor XIII L34 (FXIII-A L34) alleles with myocardial infarction (MI) have yielded conflicting results. Complicated gene-gene interactions, small sample sizes and heterogeneous genetic and environmental backgrounds may contribute to conflicting results. Simultaneous analysis of multiple gene variants in a large sample size from a genetically isolated population may overcome these weaknesses. Genotyping was performed in 500 MI patients and 500 controls from the genetically isolated Newfoundland population to determine the prevalence of the FII 20210A, FVL and FXIII-A L34 variants and association with MI. Gene-gene interactions were also analyzed. The prevalence of the FII 20210A allele was higher in MI patients (3.2%) than in controls (1.0%; P=0.015). The FII 20210A allele was also 5.6 fold higher in MI patients younger than 51 years compared with age-matched controls (P=0.04). FVL showed 3.9-fold higher prevalence in young patients than older (>50 years) patients (P = 0.004), and 2.7-fold higher than age-matched controls (P =0.007). Furthermore, the prevalence of combined carriers of the FXIII-A L34 and FII 20210A alleles was 12-fold higher in MI patients compared with controls (P = 0.002) and with 92% penetrance. There was disequilibrium of the FXIII-A L34 allele to MI patients carrying the FII 20210A allele as a genetic background. Based on our data, 1) the FII 20210A allele is a risk factor for MI, possibly important for early onset; 2) FVL may predispose for early onset MI; 3) the FXIII-A L34 allele predisposes for MI in males only; however, 4) interaction between the FII 20210A and FXIII-A L34 alleles form a synergistic co-effect which strongly predisposes for MI, placing combined carriers at high risk for MI. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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