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

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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.

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Authors and Affiliations

  1. Stroke Clinic, National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez, Insurgentes Sur 3877 Col. La Fama, C.P. 14269, Mexico, Mexico

    Angélica Ruiz-Franco, Miguel A. Barboza, Nayelli Arguelles-Morales, Juan-Camilo Vargas-González, Alejandro Quiroz-Compean & Antonio Arauz

  2. Genetics Department, National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez, Mexico, Mexico

    Aurelio Jara-Prado

  3. Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de Mexico (UNAM)-Instituto Nacional de Medicina Genómica (INMEGEN), Mexico, Mexico

    Samuel Canizales-Quinteros & Paola Leon-Mimila

Authors
  1. Angélica Ruiz-Franco
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  2. Miguel A. Barboza
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  3. Aurelio Jara-Prado
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  4. Samuel Canizales-Quinteros
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  5. Paola Leon-Mimila
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  6. Nayelli Arguelles-Morales
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  7. Juan-Camilo Vargas-González
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  8. Alejandro Quiroz-Compean
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  9. Antonio Arauz
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Correspondence to Miguel A. Barboza.

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Conflicts of interest

Dr. Ruiz-Franco reported no conflict of interest disclosure. Dr. Barboza reported no conflict of interest disclosure. Dr. Jara-Prado reported no conflict of interest disclosure. Dr. Canizales-Quinteros reported no conflict of interest disclosure. Dr. Leon-Mimila reported no conflict of interest disclosure. Dr. Arguelles-Morales reported no conflict of interest disclosure. Dr. Vargas-González reported no conflict of interest disclosure. Dr. Quiroz-Compean reported no conflict of interest disclosure. Dr. Arauz had served as a research adviser for Boehringer-Ingelheim and Pfizer.

Funding/support

This research was partially supported by the Centro Nacional de Ciencia y Tecnología (CONACYT) FONSEC 181359 Educational Grant in México.

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Ruiz-Franco, A., Barboza, M.A., Jara-Prado, A. et al. TGFBR2 mutation and MTHFR-C677T polymorphism in a Mexican mestizo population with cervico-cerebral artery dissection. J Neurol 263, 1066–1073 (2016). https://doi.org/10.1007/s00415-016-8101-8

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  • DOI: https://doi.org/10.1007/s00415-016-8101-8

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