The AT1R+1166A/C polymorphism *C allele was associated with increased MI risk (OR 1.13, p=0.005), but large between-study heterogeneity and bias suggest such genetic associations may be unreliable.
Meta-Analysis (n=27,309)
Are candidate genetic polymorphisms truly associated with an increased risk of myocardial infarction, or are the associations subject to bias?
Many formally significant genetic associations for myocardial infarction in meta-analyses may be driven by bias rather than true genetic effects, emphasizing the need for large-scale, rigorous validation.
Effect estimate: OR 1.13
p-value: p=0.005
Several genetic polymorphisms have been proposed to be associated with myocardial infarction (MI). The authors examined the evidence and biases underlying such associations using a case-study meta-analysis and an overview of large-scale data. In a meta-analysis of 27 studies addressing the association of the angiotensin type 1 receptor (AT1R)+1166A/C polymorphism with MI (10,180 cases, 17,129 controls), the *C allele conferred an increase in MI risk (odds ratio = 1.13 per allele, p = 0.005). However, there was large between-study heterogeneity; the largest study showed no effect, contradicting smaller studies; and studies with blinded genotyping showed no effect. The authors conducted an overview of meta-analyses of genetic associations for MI or coronary artery disease, including at least three studies and 3,000 subjects. In their latest meta-analysis, another 14 polymorphisms were found to have formally significant associations. If true, these associations would already explain 42% of the MI risk for Caucasian populations. Significant between-study heterogeneity was common. Across the 32 largest studies, only two found formally significant results (nine would be expected if each meta-analysis showed a true association). Even with large-scale evidence from meta-analyses, significant associations for MI may be subject to bias. Large-scale single studies and prospective consortia should be used for detecting and validating the genetic determinants of MI.
Ntzani et al. (Thu,) conducted a meta-analysis in Myocardial infarction (n=27,309). AT1R+1166A/C polymorphism (*C allele) vs. Non-carriers / other alleles was evaluated on Myocardial infarction risk (OR 1.13, p=0.005). The AT1R+1166A/C polymorphism *C allele was associated with increased MI risk (OR 1.13, p=0.005), but large between-study heterogeneity and bias suggest such genetic associations may be unreliable.