Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction

Studies associating the prothrombin 20210G > A (FII 20210A), factor V Leiden (FVL), and factor XIII Leu34 (FXIII-A Leu34) 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 opposing findings. Simultaneous analysis of multiple gene variants in a large sample size from,a genetically isolated population may overcome these weaknesses. Genotyping was performed patients and 50,0 control sub-in 06 MI. jects from the genetically isolated Newfoundland population to determine the prevalence of the FII 20210A, FVL and FXIII-A Leu34 variants and their association with MI. Gene-gene interactions were. also. analyzed. The prevalence of the Fill 20210A allele was high er in MI patients (3.2%) than in control subjects (1.0%; P = .015). The FII. 20210A allele was also 5.6-fold higher in MI patients younger than 51 years than in age-matched control subjects (P = .04). FVL showed 3.9-fold higher prevalence in young patients than in patients older than 50 years (P = .004) and 2.7-fold higher than in age-matched control subjects (P = .007). Furthermore, the prevalence of combined carriers of the FXIII-A L34 and FII 20210A alleles was 12-fold higher in MI patients than in control subjects (P = .002) and with 92% penetrance. There was disequilibrium of the FXIII-A Leu34 allele to MI patients carrying the MI 20210A allele as a genetic background. Based on our data, we determined that (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 Leu34 allele predisposes for MI in males only; however, (4) interaction between the FII 20210A and FXIII-A Leu34 alleles forms a, synergistic coeffect that I strongly. predisposes for MI, placing combined carriers at high risk for MI. (C) 2003 by The American Society of Hematology.