Resumen de Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos

M.C. Jiménez-González, David Santiago Germán, E.F. Castillo-Henkel, J. A Alvarado-Moreno, J. Hernández-Juárez, Alfredo Leaños Miranda, Abraham S. Majluf Cruz, Irma Isordia Salas

• Resumen Introducción Diversos polimorfismos en genes candidatos que codifican proteínas del sistema hemostático se han propuesto como factores de riesgo para el desarrollo de trombosis. Métodos Casos y controles, sobrevivientes de enfermedad vascular cerebral (EVC) isquémica idiopática≤45 años de edad del servicio de neurología incluidos de manera consecutiva de 2006 a 2014. Por PCR-RFLP se identificaron los polimorfismos: Thr325Ile y Ala147Thr del gen de TAFI, 4G/5G del gen de PAI-1, PLA1/A2 del gen de la glucoproteína plaquetaria IIb/IIIa, Glu298Asp del gen de eNOS, y C677T del gen de la 5,10 MTHFR. Se realizó un análisis multivariado de regresión logística para calcular el riesgo independiente de EVC. Resultados Doscientos cuatro casos y 204 controles pareados por edad y sexo. Se asoció al polimorfismo Glu298Asp (genotipo p=0,001 y frecuencia alélica p=0,001), C677T (genotipo p=0,01), hipertensión (p=0,03) y tabaquismo (p=0,02) con la presencia de EVC isquémico, no así para los polimorfismos Ala147Thr, Thr325IIe, 4G/5G y PLA1/A2. Se identificó como factor de riesgo independiente al alelo 298Asp (p=0,03), T (p=0,01), hipertensión (p=0,03), tabaquismo (p=0,01) y AHFEAT (p=0,04). Conclusiones Los polimorfismos Glu298Asp y C677T de los genes que codifican a la enzima eNOS y 5,10 MTHFR, tabaquismo, hipertensión y AHFEAT se asociaron a la presencia de EVC isquémico en jóvenes mexicanos, no así el Thr325Ile, Ala147Thr, 4G/5G, PLA1/A2 en genes que codifican proteínas del sistema de fibrinólisis y receptores plaquetarios. Introduction Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. Methods We performed a case-control study of consecutive ischaemic stroke survivors aged ≤ 45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. Results 204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. Conclusions The polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.