TGFBR2 mutation and MTHFR-C677T polymorphism in a Mexican mestizo population with cervico-cerebral artery dissection

Abstract

Spontaneous cervico-cerebral artery dissection (CCAD) is a common condition found among young patients with ischemic stroke. We examined the possible association between the polymorphism of methylenetetrahydrofolate reductase (MTHFR)-C677T and the gene mutation in transforming growth factor beta receptor II (TGFBR2) in a cohort of CCAD patients. One-hundred CCAD cases (65 males; mean age: 38.08 ± 10.68 years) and 100 matching controls were included. Ancestry informative markers (AIMs) were used to increase internal validity of the genetic analysis. Genotypes of the C677T polymorphism in the MTHFR gene were determined by polymerase chain reaction and restriction fragment length polymorphism; direct sequencing was used for a mutation analysis of the TGFBR2 gene. Associations were evaluated using a multivariate statistics, and Hardy-Weinberg equilibrium was analyzed. We also incorporated our data into a meta-analysis of the MTHFR-C677T. Sixty-three patients presented with vertebral and 37 with carotid artery dissection. Ancestry markers found a call rate on each over 95 %. All AIMs did not deviate from Hardy-Weinberg equilibrium (p > 0.05). The homozygous TT genotype was more frequent in cases (OR 2.04, CI 95 % 1.53-2.72, p = 0.005), whereas no significant difference was found on heterozygous CT genotype. TGFBR2 mutation was not present in our samples. In the meta-analysis of MTHFR/C677T variant, a total 613 cases and 1547 controls were analyzed; we found a moderate association for the recessive model genotype (OR 2.04, CI 95 % 1.53-2.72; p = 0.342; Z = 4.83; I (2) = 11.3). This study supports a positive association between the MTHFR-C677T polymorphism and genetically confirmed Mexican mestizo CCAD patients.

Keywords: Ancestry studies; C677T-MTHFR polymorphism; Cervico-cerebral artery dissection; Hyperhomocysteinemia; Ischemic stroke; Methylenetetrahydrofolate reductase; TGFBR2 gene mutation.