Approved Research

Investigating the effects of caloric restriction by utilizing loss of function variants in the PLA2G7 gene as a proxy- A UK biobank study

Lay summary

Costly and unsuccessful clinical trials can be avoided by associating genes with the risk of certain diseases. One example is darapladib, a drug that was previously developed to improve health outcomes of individuals at risk of cardiovascular diseases. Previous studies supported its ability to reduce lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, which is proposed to be a driver of cardiovascular diseases. However, darapladib was unsuccessful in reducing the risk of cardiovascular clinical end points. In fact, these findings were later found to be reflected in genetic epidemiological studies. Genetically lowered Lp-PLA2 activity, were not associated with decreased risk of coronary events. Nonetheless, given the biological significance of Lp-PLA2 in different diseases, darapladib is likely to have other clinical benefits. Since Lp-PLA2 activity can be altered genetically and through darapladib, parallels can be drawn to search for novel relationships between other traits.