Dissecting the genetic determinants of hemostasis and thrombosis

Abstract

Purpose of Review New DNA genotyping and sequencing technologies have facilitated the rapid advancement in our knowledge of human genomic variation and a search for the heritable determinants of complex genetic traits. This review highlights findings from recent genetic studies of complex traits primarily related to venous thromboembolism and provides tools to understand and interpret genome-wide association studies and next generation sequencing studies. Recent Findings Genome-wide studies of venous thromboembolic disease and the variation of the protein components of the hemostatic system have been reported. The results of these studies have suggested that variants in a diverse set of known and new genes contribute to the heritability of these traits but that many of the genetic determinants of these traits still remain undiscovered. Summary Next generation sequencing studies and functional studies of the gene loci that contribute to hemostatic traits are currently underway. Future studies that explore the role of rare genetic variants, regulatory elements of the genome and gene-gene interactions will be required for a more complete understanding of the genetic control of the hemostatic system and for the application of this knowledge to the care of patients with disorders of thrombosis and hemostasis.

Ten things to know about ten cardiovascular disease risk factors

“…Among the more common inherited causes of CVD in younger individuals include genetic abnormalities leading to vasculopathies, aneurysmal disorders, cardiomyopathies, and coagulopathies. [ 190 , 352] Genetic abnormalities can also lead to CVD risk factors such as diabetes mellitus [353] and hypertension. [354] Other genetic abnormalities leading to CVD includes inherited dysrhythmia syndromes and genetic dyslipidemias.…”

Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays

“…The relevance of genetic factors in thrombosis and their high heritability have been proven to a great degree by the description of thrombophilic families. 24,25 Since the discovery of antithrombin deficiency in 1965, hundreds of studies have tried to identify new gene defects increasing the risk of thrombosis. In the 1980s, the study of families with thrombophilia and intermediate phenotypes in the hemostatic system allowed the identification of congenital protein C and protein S deficiencies as another class of strong dominant thrombophilias.…”

Polymorphisms of candidate genes determining the clinical and hemostasiological characteristics of endocarditis of various etiology

“…Одним из перспективных направлений в создании панели маркеров риска развития тромбоэмболических осложнений при эндокардитах является исследование параметров системы гемостаза [2,3]. Гиперфибриногенемия является самостоятельным фактором, приводящим к гиперкоагуляции [4]. Изменения лейкоцитарно-тромбоцитарной агрегации и тромбоцитоз являются важнейшими нарушениями сосудисто-тромбоцитарного гемостаза, обусловливающими развитие гиперагрегации [5].…”