Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
FRONTIERS IN GENETICS
Authors: Ningtyas, Dian; Thomson, Russell J.; Tarlac, Volga; Nagaraj, Shivashankar H.; Hoy, Wendy; Mathews, John D.; Foote, Simon J.; Gardiner, Elizabeth E.; Hamilton, Justin R.; McMorran, Brendan J.
Abstract
The F2RL3 gene encoding protease activated receptor 4 (PAR4) contains a single nucleotide variant, rs773902, that is functional. The resulting PAR4 variants, Thr120, and Ala120, are known to differently affect platelet reactivity to thrombin. Significant population differences in the frequency of the allele indicate it may be an important determinant in the ethnic differences that exist in thrombosis and hemostasis, and for patient outcomes to PAR antagonist anti-platelet therapies. Here we determined the frequency of rs773902 in an Indigenous Australian group comprising 467 individuals from the Tiwi Islands. These people experience high rates of renal disease that may be related to platelet and PAR4 function and are potential recipients of PAR-antagonist treatments. The rs773902 minor allele frequency (Thr120) in the Tiwi Islanders was 0.32, which is similar to European and Asian groups and substantially lower than Melanesians and some African groups. Logistic regression and allele distortion testing revealed no significant associations between the variant and several markers of renal function, as well as blood glucose and blood pressure. These findings suggest that rs773902 is not an important determinant for renal disease in this Indigenous Australian group. However, the relationships between rs773902 genotype and platelet and drug responsiveness in the Tiwi, and the allele frequency in other Indigenous Australian groups should be evaluated.
The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction A Scientific Statement From the American Heart Association
CIRCULATION-CARDIOVASCULAR GENETICS
Authors: Musunuru, Kiran; Ingelsson, Erik; Fornage, Myriam; Liu, Peter; Murphy, Anne M.; Newby, L. Kristin; Newton-Cheh, Christopher; Perez, Marco V.; Voora, Deepak; Woo, Daniel
Abstract
There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the "expressed genome." The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias.