Homozygous methylentetrahydrofolate reductase C667T genotype anticipates age at venous thromboembolism by one decade. Issue 6 (September 2021)

• Record Type: Journal Article
• Authors: Ames, Paul R.J.; D'Andrea, Giovanna; Marottoli, Vincenzo; Iannaccone, Luigi; Caruso, Matilde; Gentile, Fabrizio; Margaglione, Maurizio
• Is Part Of: Blood coagulation and fibrinolysis. Volume 32:Issue 6(2021)
• Publication Date: 2021-09
• Subjects: age -- homocysteine -- methylentetrahydrofolatereductase -- venous thromboembolism; Blood -- Coagulation -- Periodicals; Fibrinolysis -- Periodicals; Hemostasis -- Periodicals; Thrombosis -- Periodicals; Blood Coagulation -- Periodicals; Fibrinolysis -- Periodicals; Hemostasis -- Periodicals; Thrombosis -- Periodicals; 612.115
• DOI: 10.1097/MBC.0000000000001049
• Languages: English
• ISSNs: 0957-5235

Abstract

Abstract : N/A: The aim of the study was to compare age at first venous thromboembolism (VTE), plasma homocysteine and activated partial thromboplastin time ratio (aPTTr) amongst unprovoked VTE patients with the methylentetrahydrofolate reductase (MTHFR) C667T genotypes, and to identify predictors of age at first VTE, of plasma homocysteine and of the aPTTr; to evaluate whether heterozygous or homozygous prothrombin (PT) G20210A mutation lowered the age at first VTE when associated with MTHFR TT. Retrospective cohort study on 259 MTHFR TT, 76 MTHFR TC and 64 MTHFR CC participants with unprovoked VTE; each participant contributed age, sex, age at VTE, history of dyslipidaemia, hypertension, smoking, homocysteine (measured by enzyme immunoassay) and aPTTr (measured by standard coagulation assay). Age at first VTE was lower in MTHFR TT than MTHFR TC and CC (41 ± 14 vs. 50 ± 16 vs. 51 ± 12 years, respectively, P < 0.0001); plasma homocysteine was higher in MTHFR TT than in the other groups (22 ± 21 vs. 12 ± 11.6 vs. 10 ± 3.3 μmol/l, respectively, P = 0.0005) whilst aPTTr was not different. MTHFR TT independently predicted age at first VTE ( P = 0.001), plasma homocysteine ( P < 0.0001) alongside sex ( P = 0.0007), age and smoking ( P = 0.03 for both). Compound MTHFR TT with PT GA or AA had no lowering effect on age at first VTE compared with MTHFR TT alone (41 ± 13 vs. 41 ± 14 years). Plasma homocysteine inversely related to aPTTr in the MTHFR TT group ( P = 0.003). MTHFR TT anticipates age at first VTE by an average of 10 years compared with MTHFR TC and CC genotypes.