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The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke

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Abstract

Previous studies have suggested that both angiotensin II type-1 receptor (AT1R) 1166C and methylenetetrahydrofolate reductase (MTHFR) 677T variants can have disadvantageous effects on the small-vessel circulation under certain conditions. The purpose of this study was to analyze the possible consequences of the simultaneous distribution of these two genetic variants in different types of ischemic stroke. The genetic and clinical data on 357 ischemic stroke patients and 263 control subjects were analyzed by using univariate and logistic statistical approaches. Neither the MTHFR677T nor the AT1R 1166C genetic variant alone conferred the risk of any subtype of ischemic stroke. The combination of the homozygous MTHFR 677TT genotype and at least one AT1R 1166C allele occurred more frequently in the ischemic stroke patients (8.68%) than in the controls (4.56%, p<0.05). Specific subclassification of the patients revealed an accumulation of this combination in small-vessel-associated ischemic stroke (12.2%, p<0.01); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.66 (95% confidence interval, 1.28–7.89; p<0.05). These findings suggest that the combination of these two genetic factors can contribute to the development of small-vessel cerebral infarcts. Although the exact mechanism of action is not known, addition of the unfavourable effects on the endothelial function can be presumed.

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Authors and Affiliations

  1. Department of Neurology and Neurophysiology, Pandy Kalman County Hospital, Gyula

    Zoltan Szolnoki, Andras Kondacs & Mihaly Szabo

  2. Department of Medical Genetics and Child Development, University of Pecs, Pecs

    Anita Maasz, Lili Magyari, Katalin Horvatovich, Bernadett Farago & Bela Melegh

  3. Central Laboratory, Pandy Kalman County Hospital, Gyula

    Ferenc Somogyvari

  4. Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Szeged, Szeged

    Ferenc Somogyvari

  5. Department of Pathology, Rethy Pal County Hospital, Bekescsaba, Hungary

    Anita Bodor

  6. Central Laboratory, Markusovszky Teaching Hospital, Szombathely, Hungary

    Ferenc Hadarits

  7. MTA-PTE Clinical Genetics Research Group of the Hungarian Academy of Sciences, University of Pecs, Pecs, Hungary

    Bela Melegh

Authors
  1. Zoltan Szolnoki
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  2. Anita Maasz
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  8. Mihaly Szabo
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  9. Anita Bodor
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  11. Bela Melegh
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Correspondence to Zoltan Szolnoki.

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Szolnoki, Z., Maasz, A., Magyari, L. et al. The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke. J Mol Neurosci 31, 201–207 (2007). https://doi.org/10.1385/JMN:31:03:201

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  • DOI: https://doi.org/10.1385/JMN:31:03:201

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