Ischemic cerebrovascular stroke (IS) is a polygenic multifactorial disease; effect of thrombotic gene polymorphism, platelet activation and reactivation synergistic risk effect are plausible postulation.
To assess synergistic effect of FVL and MTHFR genes polymorphisms and platelet activity and reactivity as risk factors for ischemic cerebrovascular stroke
A hospital-based case-control study; approvered by Suez Canal University (SCU) ethical committee, after obtaining an informed consent. 120 individuals were included: 60 acute IS patients, subdivided into 2 subgroups regarding the vascular risk factors recruited from neurology department, SCU Hospital; and 60 matched healthy individuals. FVL G1691A, FVLA4070G, FVL A5279G, MTHFRC677T, and MTHFR A1298C were assessed using multiplex real-time PCR assay (AnyplexTM II Thrombosis SNP Panel Assay, seegene); platelet ex vivo activity & reactivity (CD62P; after ADP provocation) were assessed by four-colors flow cytometry, FACS Caliber, BD-Biosciences).
Both FVLG1691A & FVL A4070G (OR 19.6; 95 % CI = 2.5 to 154.4; p = 0.0001), (OR 7.6; 95 % CI = 1.13 to 178; p = 0.012), and MTHFRC677T (OR 10; 95 % CI = 1.16to 85.8; p = 0.03) and MTHFRA1298C (OR 11.6; 95 % CI = 1.35to 100.7; p = 0.03) & the presence of >1 mutation (p < 0.0001) showed a statistically significant association with IS. Multivariate logistic regression models showed that studied SNPs add synergistic effect on the vascular risk factors. A statistically significant difference was detected in platelet CD62p % after adding ADP (IS patients: 72.95 ± 14.8 - controls: 62.2 ± 11.39), MFI IS patients: 248 ± 101-controls 215 ± 75.8). both FVLG1691A and MTHFRC677T were significantly associated with higher baseline platelet activation in the co-dominant and recessive models for FVLG1691A and in the dominant model for MTHFRC677T
FVLG1691A, FVL14070G, MTHFRC677T & MTHFRA1298C were independent risk factors for IS especially in younger patients & existence of >1 mutation significantly increased IS risk, platelet activity and reactivity and genetic polymorphism play a potential synergistic role increasing the risk of IS.