Impact of plasma homocysteine and prothrombin G20210 A on primary antiphospholipid syndrome

The prevalence of prothrombin (PT) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677 <-- T was assessed in 40 patients with primary antiphospholipid syndrome (APS) (14 male, 26 female; mean age, 37 +/- 14 years) and in 27 persistent carriers of antiphospholipid antibodies (aPL) (five male, 22 female; mean age, 40 +/- 16 years) without underlying diseases. Non-APS thrombotic patients (n = 100; 47 female, 53 male; mean age, 40 +/- 10 years) and healthy subjects (n = 100; 46 female, 54 male; mean age, 56 +/- 16 years) served as control groups. Plasma homocysteine (HC) (enzyme-linked immunosorbent assay) was measured in all aPL patients and in 51 subjects from the healthy control group (mean age, 38 +/- 16 years). Heterozygous prothrombin PT G20210A was more frequent in the thrombotic group without APS (18%) than in the control (4%), APS (12%) or aPL (11%) groups, whereas homozygous MTHFR C677 <-- T was equally distributed. After genotype sub-grouping, plasma HC was higher in APS patients with homozygous MTHFR C677 <-- T compared with non-homozygous APS patients (22 +/- 5.4 versus 11 +/- 1.3 micromol/l; P < 0.01) and with homozygous MTHFR C677 <-- T controls (22 +/- 5.4 versus 15 +/- 2.0 micromol/l). In the APS group, mean age at first event was lower in homozygous MTHFR C677 <-- T patients than in non-homozygous patients (26 +/- 7.5 versus 36 +/- 13 years; P = 0.008). In the same group, homozygous MTHFR C677 <-- T patients suffered an increased average number of events per person than non-homozygous patients (1.9 versus 1.3; P = 0.04). Heterozygous PT G20210A contributes little to the thrombotic tendency of primary APS whereas plasma HC may influence age at first event and number of events. Measurement of plasma HC in aPL subjects may identify patients at increased thrombotic risk requiring HC lowering.