title: [C677T mutation in methylentetrahydrofolatereductase gene in patients with venous thromboses from the central region of Russia correlates with a high risk of pulmonary artery thromboembolism].
abstract: OBJECTIVE
  To investigate genetic factors of risk (RF) to develop venous thrombosis and pulmonary artery thromboembolism (PATE) in population of central Russia.
  
  
  METHODS
  We studied polymorphism of the genes of coagulation factor II (G20210A), factor V (G1691A) and methylentetrahydrofolatereductase (MTHFR) with polymerase chain reaction and restriction analysis of DNA amplified sites. We estimated prevalence of the mutations in healthy population and in patients with flebothrombosis as well as effects of the mutations on a PATE rate in patients with thrombosis. We examined 97 patients with documented flebothrombosis. PATE was detected in 54 of them. The control group consisted of 56 healthy volunteers matched by age and gender.
  
  
  RESULTS
  G1691A mutation in the gene of coagulation factor V (Leiden mutation of factor V--LMFV) in healthy population occurred in 3.6%, in patients with flebothromboses--in 19.6% (OR = 6.58; 95% CI from 1.47 to 29.42; p = 0.006). Heterozygous mutation G20210A in prothrombine gene was detected in 8 (8.2%) patients (p = 0.027), while this mutation was registered in none controls. Polymorphism of MTHFR gene (C677T) was seen both in the control and patients (60.7 and 52.6%, respectively). LMFV occurrence in patients with flebothrombosis and PATE is less than in patients with flebothrombosis without TEPA (16.7 and 23%, respectively). The PATE risk is significantly higher in carriers of mutant allele 677CT and 677TT of MTHFR compared to patients free of this mutation (OR = 3.11; CI 95% from 1.35 to 7.15; p = 0.006). Homozygous inheritance of this mutation in males combined with PATE in 100% cases. Of 8 carriers of heterozygous mutation G20210A in prothrombin gene PATE was detected in 5 carriers.
  
  
  CONCLUSIONS
  LMFV and mutation G20210A in prothrombin gene are genetic risk factors of venous thrombosis. LMFV is not a PATE risk factor. Mutation C677T in MTHFR gene has no influence on the risk of venous thromboses but makes PATE much more probable. This suggests that it may be a genetic risk factor of PATE in this disease.
authors.forename: P V
authors.initials: PV
authors.lastname: Avdonin
authors.forename: A I
authors.initials: AI
authors.lastname: Kirienko
authors.forename: L M
authors.initials: LM
authors.lastname: Kozhevnikova
authors.forename: N A
authors.initials: NA
authors.lastname: Shostak
authors.forename: N M
authors.initials: NM
authors.lastname: Babadaeva
authors.forename: S G
authors.initials: SG
authors.lastname: Leont'ev
authors.forename: E B
authors.initials: EB
authors.lastname: Petukhov
authors.forename: A A
authors.initials: AA
authors.lastname: Kubatiev
authors.forename: V S
authors.initials: VS
authors.lastname: Savel'ev
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002391:Catchment Area, Health; D005165:Factor V; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics; D011655:Pulmonary Embolism / Q000235:genetics*; D018570:Risk Assessment; D012426:Russia
chemical_list: D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)