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APOE and AGT in the Finnish p.Arg133Cys CADASIL population

M Siitonen1,2, K Mykkänen1, F Pescini3

  • 1Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.

Acta Neurologica Scandinavica
|March 31, 2015
PubMed

Insights

Genetic factors like APOE, AGT, and NOTCH3 polymorphisms do not influence stroke or migraine onset in Finnish CADASIL patients. Further research is needed to understand CADASIL

Area of Science:

  • Neurology
  • Genetics
  • Vascular Biology

Background:

  • Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic small vessel disease impacting brain vasculature and causing vascular dementia.
  • Over 230 mutations in the NOTCH3 gene are linked to CADASIL, presenting with highly variable clinical symptoms, even within families.
  • Previous research suggests that additional genetic factors may influence the manifestation of CADASIL phenotypes.

Purpose of the Study:

  • To investigate potential associations between specific genetic polymorphisms and the clinical presentation of CADASIL.
  • To analyze the impact of apolipoprotein E (APOE) genotype, angiotensinogen (AGT) p.Met268Thr polymorphism, and NOTCH3 p.Ala202Ala polymorphism on the age of first-ever stroke or migraine in Finnish CADASIL patients.

Main Methods:

  • Analysis of 134 Finnish patients diagnosed with CADASIL carrying the p.Arg133Cys NOTCH3 mutation.
  • Genotyping for apolipoprotein E (APOE) and angiotensinogen (AGT) polymorphisms.
  • Assessment of a neutral NOTCH3 polymorphism (p.Ala202Ala).

Main Results:

  • No statistically significant association was found between APOE genotypes and the onset of stroke or migraine in the study cohort.
  • The angiotensinogen (AGT) p.Met268Thr polymorphism showed no correlation with earlier onset of stroke or migraine.
  • The neutral NOTCH3 p.Ala202Ala polymorphism was not associated with modified onset of stroke or migraine in CADASIL patients.

Conclusions:

  • APOE, AGT, and NOTCH3 polymorphisms do not appear to modify the clinical onset of strokes or migraine in this large, mutationally homogeneous CADASIL cohort.
  • The findings underscore the complexity of CADASIL's variable phenotype, suggesting other genetic or environmental factors may be involved.
  • International collaboration and large-scale, genome-wide studies are recommended to identify the genetic modifiers of CADASIL.
Abstract

Keywords:
AGTAPOECADASILNOTCH3association studyfounder effectgenotype-phenotype correlation

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