Akademik Veri Yönetim Sistemi
INSAC - Natural and Health Sciences 2020 (INHS-2020), İstanbul, Türkiye, 22 - 23 Mayıs 2020, ss.104-106, (Tam Metin Bildiri)
Thrombophilia is a term used to describe the factors that cause thrombosis. Thrombosis development is multifactorial caused by many acquired and hereditary factors. While endothelial damage and functional disorders of platelets play an important role in the arterial system; in the venous system, mostly stasis and disorders of the coagulation system cause the development of thrombosis. Thrombophilia term is considered in the context of venous thromboembolism (VTE). VTE is a serious health problem that affects 1-2 of every 1000 people. VTE is the main cause of pregnancy-related mortality and morbidity.
FV-Leiden mutation (G1691A) is the most common cause of hereditary thrombophilia in Caucasians (2-15%). As the amount of Factor V elevated, the tendency to thrombosis increases.
FII-G20210A mutation is the second most common hereditary risk factor for VTE, and the risk of venous thrombosis increases 3 times. While it is approximately 2%-4% heterozygous in Caucasians, rare in Africans and Asians. The FIIG20210A mutation increases its amount in plasma by increasing prothrombin synthesis.
MTHFR C677T polymorphism is 30-40% heterozygous and 10-13% homozygous in whites. This polymorphism is thermolabile variant of the MTHFR enzyme. Another common mutation is MTHFR A1298C. Heterozygous individuals for both mutations can create a clinical picture similar to homozygous C677T. Hyperhomocysteinemia was observed in women with two or more abortions, placental embolism, and children with fetal growth retardation.
There is a common polymorphism known as 4G/5G in the plasminogen activator inhibitor-1 gene (PAI-1). Since PAI-1 acts as main inhibitor of fibrinolysis, high levels of PAI-1 may be associated with the risk of arterial thrombosis. In the case of congenital PAI-1 deficiency, it might lead to hemorrhagic diathesis. High PAI-1 levels in various forms of cancer, obesity, and metabolic syndrome are associated with increased thrombosis formation.
Fibrinogen-beta (FGB) gene encodes the beta chain subunit of fibrinogen. -455AA allele carriers have higher fibrinogen levels. There are studies related to myocardial perfusion, pulmonary embolism, C-reactive protein levels. Mutations in FGB gene can cause excessive bleeding or thrombosis due to functional change.
We evaluated the results of those, applied thrombophilia panel analysis in our molecular genetics laboratory, among the patients admitted/referred to Cerrahpasa Medical Faculty Genetic Diseases Diagnosis Center (GETAM) outpatient clinic with thrombophilia pre-diagnosis. 500 patients were included in the study; 377 are women (27.4%) and 123 are men (24.6%). The thrombophilia panel studied in our center contains 6 gene regions of 5 genes. These gene regions are: MTHFR C677T and MTHFR A1298C regions, FII-Prothrombin G20210A region, FV-Leiden R506Q, 4G/5G region in PAI-1 gene promoter, FGB gene -450C/T region.
Blood of the patients were withdrawn into the tubes with EDTA and DNA isolations were performed. The panel study performed with Applied Biosystems ABI PRISM® sequencing and analysis system. The kit works with fluorescent system that allows multiplex amplification/ligation in the same tube for automated SNP analysis. Fluorochromes include FAM, JOE, ATTO550 and ATTO565.
Since the diseases and complaints, related to thrombophilia, varied, the cases included in the study were directed to our center with many different indications, and these cases were evaluated based on the variants of the genes studied in the panel, not according to the indication. When genetic panel test indications are examined, it is seen that habitual abortion is prominent especially with 206 (41.2%) cases. Among other indications; 48 (9.6%) deep vein thrombosis, 34 (6.8%) pulmonary thromboembolism, 25 (5%) cerebrovascular disease, 22 (4.4%) suspicion of thrombophilia, 14 (2.8%) infertility/IVF failure, 11 (2.2%) stroke/ischemic stroke, FV mutation in 5 (1%) families, 5 (1%) Behçet's Disease.
When the results of the thrombophilia panel studied in our center are evaluated; in the MTHFR gene, of the 500 cases, 247 (49.4%) were 677C normal, 53 (10.6%) were homozygous mutants, and 200 (40%) heterozygous alleles. In the MTHFR gene, 202 (40.4%) of the 500 cases were normal for A1298C variant, 66 (13.2%) were homozygous mutants and 232 (46.4%) were heterozygous alleles. For G20210A polymorphism in the Factor-II Prothrombin gene, 465 (93%) of 500 cases were normal, 33 (6.6%) were heterozygous, and 2 (0.4%) were homozygous mutant alleles. For G1691A polymorphism in FV-Leiden R506Q mutation; of the 500 cases, 414 (82.8%) were normal, 77 (15.4%) were heterozygous and 9 (1.8%) were homozygous mutant allele. For 4G/5G polymorphism in the promoter region of the PAI-1 gene, 131 of 500 cases (26.2%) were normal, 128 (25.6%) were homozygous mutants and 241 (48.2%) were heterozygous allele. In terms of FGB gene -455 polymorphism; of the 500 cases, 303 (64.2%) were normal, 142 (30%) were heterozygous, 27 (5.7%) had homozygous mutant alleles.