Factor V Leiden and Prothrombin G20210a Mutations in Young Adults with Ischemic Stroke.
Authors: De Ona Raquel , Llamas Pilar , De Velasco Jaime Fernandez , Santos Ana Belen , Meseguer Elena , Garcia-Raso Arancha , Tomas Jose Francisco 
Published: April 2020

Ischemic stroke (IS) is a multifactorial disease caused by interaction of genetic and environmental factors. Conventional vascular risk factors contribute less to IS in young adults than to stroke in the elderly. Attempt to detect relatively weak thrombophilic risk factors appears most promising in young patients with IS. Factor V Leiden (FVL) and the prothrombin (PT) G202110A mutation are relatively common in caucasian populations and contribute to a thrombophilic phenotype. Nevertheless, a very large variability in the prevalence of both mutations has been observed in different ethnic groups and the evidence of a role for these gene variants in the risk of IS is controversial.

Patients and methods: Genotypic analyses were performed on 308 consecutive unrelated patients diagnosed with IS, 147 women and 161 men, mean age 700.8 years, who were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment. All included cases were age and sex matched to a control from the same geographic area who had no history of vascular disease. In the study, 92 patients (29,8%) and 83 control (26,9%) were youngers than 66 years. Patients and controls completed a questionnaires including blood pressure, diabetes status, total serum cholesterol level and smoking history. Genetic tests were performed by RFLP-PCR. The strength of the association of the polymorphisms with the occurrence of IS was estimated by calculation of the OR and its 95%CI by exact method. P values less than 0.05 were considered significant. SPSS 9.0 was used for statistical analysis.

Results: FVL was present in 1,6% of IS patients (n= 5) compared with 3,9% of controls (n= 12). Only one of the 5 patients carriers of mutation was homozygous. This finding corresponds to an odds ratio (OR) for adult IS of 0,4 (95%CI: 0,14–1,16;p= 0,084). When we analysed the prevalence of FVL according to age, we observed that in patients younger than 65 years was 2,2% compared with 1,2% in controls (OR: 1,82;95%CI: 0,13–51,76;p= 0,928). In patients older than 65 years prevalence was 1,4% compared with 4,9% in controls (OR: 0,27;95%CI: 0,06–1,07;p= 0,067). After adjustment for age, odds ratio for IS was 0,41 (95%CI: 0,12–1,28;p= 0,146). PT 20210A mutation was present in 4,6% of IS patients (n= 14) compared with 4,3% of controls (n= 13) (OR: 1,06;95%CI: 0,49–2,3;p= 0,871). When we analysed prevalence of PT 20210A mutation according to age, we observed that in patients younger than 65 years was 5,4% compared with 1,2% in controls (OR: 4,71;95%CI: 0,52–108,90;p= 0,214). In patients older than 65 years prevalence was 4,2% compared with 5,4% in controls (OR: 0,72;95%CI: 0,27–1,88;p= 0,537). After adjustment for age, OR was 1,04 (95%CI: 0,45–2,39;p= 0,914). Genetics analysis in relation with FVL and PT 20210A mutation were similar for the different subtypes of IS. In the distribution of conventional risk factors, cases were more often hypertensives (OR: 1,68; p= 0,001); diabetics (OR: 2,28; p&lt; 0,001), current smokers (OR: 1,77; p= 0,004), and hiperlipidemics (OR: 1,52; p= 0,033).

Conclusions: Our results suggest that in Spanish population, the PT20210 mutation is a risk factor for IS in adults younger than 65 years. In addition, our findings suggest that the frequency of FVL in elderly individuals with IS may actually be lower than in controls and it might be a protective factor against IS in older patients.