Prothrombin G20210A

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Prothrombin G20210A
'factor II mutation, prothrombin mutation
Classification and external resources
OMIM 176930#0009
DiseasesDB 32790

Prothrombin G20210A refers to a human gene mutation that increases the risk of blood clots.

The "G20210A" refers to the fact that the mutation is a guanine (G) to adenine (A) substitution at position 20210 of the DNA of the prothrombin gene. This mutation (or more accurately, single-nucleotide polymorphism or variant), is commonly associated with increased risk of occurrence and recurrence of the disease venous thromboembolism (VTE), including both deep vein thrombosis (DVT) and pulmonary embolism (PE). As of 2005, it was believed that most carriers of the mutation never develop VTE in their lifetimes.[1][needs update] Other blood clotting pathway mutations that increase the risk of clots include factor V Leiden.

Prothrombin G20210A was identified in the 1990s, is almost exclusively present in Caucasians.[1] It is estimated to have originated in that population slightly over 20,000 years ago.[2][better source needed] About 2 to 3% of Caucasians carry the variant.[3][needs update]

Signs and symptoms[edit]

The variant causes elevated plasma prothrombin levels (hyperprothrombinemia),[4] possibly due to increased pre-mRNA stability.[5] Prothrombin is the precursor to thrombin, which plays a key role in causing blood to clot (blood coagulation). G20210A can thus contribute to a state of hypercoagulability, but not particularly with arterial thrombosis.[4] A 2006 meta-analysis showed only a 1.3-fold increased risk for coronary disease.[6]

It confers a 2- to 3-fold higher risk of VTE.[clarification needed] Deficiencies in the anticoagulants Protein C and Protein S give a higher risk (5- to 10-fold).[1] Behind non-O blood type[7] and factor V Leiden, prothrombin G20210A is one of the most common genetic risk factors for VTE.[4] It was realized in 1996 that a particular change in the genetic code produces the body to make too much of the prothrombin protein. By having too much prothrombin, it increases the chances the blood clotting. Individuals who carry the condition have the prothrombin mutation which can be inherited by offspring.[8]

Having the prothrombin mutation increases the risk of developing a DVT (Deep vein thrombosis), known as a blood clot in the deep veins, often but not always in the legs.[citation needed] DVTs are threatening as they can damage the veins throughout the body, causing pain and swelling, and sometimes leading to disability.[citation needed] Most variety of people who have this prothrombin gene mutation do not require any treatment but need to be cautious throughout periods when the possibility of getting a blood clot may be enlarged (e.g. after surgery, during long flights etc.); occasionally people with the mutation may need to go on blood thinning medication to decrease the risk of developing blood clots.[9][better source needed] As there is no cure for the mutation, studies throughout the world are becoming conversant, emitting various medications in order to decrease risk factors.

Heterozygous carriers who take combined birth control pills are at a 15-fold increased risk of VTE,[3] while carriers also heterozygous with factor V Leiden have an approximate 20-fold higher risk.[1] In a recommendation statement on VTE, genetic testing for G20210A in adults that developed unprovoked VTE[a] was disadvised, as was testing in asymptomatic family members related to G20210A carriers who developed VTE.[10] In those who develop VTE, the results of thrombophilia tests (wherein the variant can be detected) rarely play a role in the length of treatment.[11]

Cause[edit]

The classical blood coagulation pathway

The polymorphism is located in a noncoding region of the prothrombin gene (3' untranslated region nucleotide 20210[b]), replacing guanine with adenine.[4][5] The position is at or near where the pre-mRNA will have the poly-A tail attached.[5]

Terminology[edit]

Because prothrombin is also known as factor II, the mutation is also sometimes referred to as the factor II mutation or simply the prothrombin mutation; in either case, the names may appear with or without the accompanying G20210A location specifier (unhelpfully, since prothrombin mutations other than G20210A are known).

Notes[edit]

  1. ^ Provoked VTE is triggered by situations such as surgery, trauma, cancer, or immobility.
  2. ^ Specifically, position 20210 refers to the nucleotide on the sense strand downstream from the DNA that codes for the start codon (ATG, positions 1 to 3).[12]

References[edit]

  1. ^ a b c d Rosendaal FR, Reitsma PH (July 2009). "Genetics of Venous Thrombosis". J. Thromb. Haemost. 7 Suppl 1: 301–304. doi:10.1111/j.1538-7836.2009.03394.x. PMID 19630821. 
  2. ^ Kniffin, Cassandra L. & McKusick, Victor A. (2012-06-20). Coagulation factor II; F2: .0009 thrombosis, susceptibility to OMIM. Accessed January 23, 2012.[better source needed]
  3. ^ a b Rosendaal FR (2005). "Venous thrombosis: the role of genes, environment, and behavior". Hematology Am. Soc. Hematol. Educ. Program. 2005 (1): 1–12. doi:10.1182/asheducation-2005.1.1. PMID 16304352. 
  4. ^ a b c d Martinelli I, Bucciarelli P, Mannucci PM (2010). "Thrombotic risk factors: basic pathophysiology". Crit Care Med. 38 (2 Suppl): S3–9. doi:10.1097/CCM.0b013e3181c9cbd9. PMID 20083911. 
  5. ^ a b c Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996). "A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis". Blood. 88 (10): 3698–703. PMID 8916933. 
  6. ^ Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, et al. (2006). "Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls". Lancet. 367 (9511): 651–8. doi:10.1016/S0140-6736(06)68263-9. PMID 16503463. 
  7. ^ Reitsma PH, Versteeg HH, Middeldorp S (2012). "Mechanistic view of risk factors for venous thromboembolism". Arterioscler Thromb Vasc Biol. 32 (3): 563–8. doi:10.1161/ATVBAHA.111.242818. PMID 22345594. 
  8. ^ Varga, E. A. (2004). "Prothrombin 20210 mutation". Circulation. doi:10.1161/01.CIR.0000135582.53444.87. 
  9. ^ Haematology, Melbourne. "Prothrombin Gene Mutation | Fact Sheets". www.melbournehaematology.com.au. Retrieved 2016-05-06. [better source needed]
  10. ^ Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2011). "Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members". Genet Med. 13 (1): 67–76. doi:10.1097/GIM.0b013e3181fbe46f. PMID 21150787. [dead link][dead link]
  11. ^ Baglin T (2012). "Inherited and acquired risk factors for venous thromboembolism". Semin Respir Crit Care Med. 33 (2): 127–37. doi:10.1055/s-0032-1311791. PMID 22648484. 
  12. ^ Degen SJ, Davie EW (1987). "Nucleotide sequence of the gene for human prothrombin". Biochemistry. 26 (19): 6165–77. doi:10.1021/bi00393a033. PMID 2825773. 

Further reading[edit]