Evaluating the use of mortuary samples to assess survival bias in myocardial infarction

Abstract

Myocardial infarction (MI) is the leading cause of death in Europe and a great financial burden on society. Whilst studies on the genetics of MI are plentiful, findings are often conflicting, with the reported effect of a genetic variant ranging from protective to deleterious or no effect. Survival bias may be a reason for these inconsistent results, necessitating a study which adequately assesses its effect on studies of MI. The aim of this project is to assess survival bias by comparing the allele frequency of variants in post-mortem formalin fixed paraffin embedded (FFPE) tissue samples from individuals who died from cardiovascular-related conditions to the allele frequency in survivors of MI. The DNA isolated from the FFPE tissue samples was not of sufficient quality to successfully carry out restriction enzyme digest, regardless of the various optimisation procedures carried out. This was not due to PCR inhibitors. The major problem was that of DNA fragmentation which was observed to increase with duration of storage. Time from death to tissue processing may also be having an effect. From data collected from the Maltese Acute Myocardial Infarction (MAMI) study on the integrin subunit beta 3 T196C (ITGB3 T196C) polymorphism (known to increase susceptibility to MI), it was noted that the allele frequency of this variant did not change with increasing age group and thus this polymorphism was not significantly affected by survival bias. Survival bias could be assessed using more sensitive techniques such as real-time PCR and next generation sequencing.