Common genetic polymorphisms in Moyamoya and atherosclerotic disease in Europeans

Abstract

Purpose  

Moyamoya is the most common cerebrovascular disease in children in Japan. The disease’s etiology is still widely unknown.
Several publications describe histopathological changes in the walls of affected vessels similar to those seen in atherosclerosis.
In this study, we analyzed the DNA of European patients with Moyamoya disease for single nucleotide polymorphisms associated
with atherosclerotic changes.

Methods  

We genotyped 17 SNPs in or adjacent to 11 genes (ELN, LIMK1, CDKN2A/B, CXCL12, Pseudogene ENSG00000197218, PSRC1, MTHFD1L,
SMAD3, MIA3, PDGF-B, TIMP2) comparing 40 DNA samples of Moyamoya disease patients to 68 healthy controls from central Europe.
The mean age of onset of Moyamoya disease (MMD)-related symptoms was 15.4 years of age. Genotyping was performed by sequencing
the SNP containing genetic regions with custom-made primers.

Results  

We found strong association of one SNP (rs599839 [A/G], OR?=?2.17, 95% CI?=?1.17, 4.05; p?=?0.01) with the risk allele G located in the 3? UTR region of the PSRC-1 gene. Three further SNPs (rs8326, rs34208922, rs501120)
in or adjacent to the genes ELN and CXCL12 showed tendencies towards risk alleles with p values between 0.1 and 0.2 but did not reach statistical significance in our cohort.

Conclusions  

Our results indicate a possible parallel of common processes in the genesis of Moyamoya disease and atherosclerotic disease.
Further analyses in larger European cohorts and replication in patients of different ethnicity may lead to possible early
detection of patients at risk for developing MMD and subsequently to future causative therapies.

• Content Type Journal Article
• DOI 10.1007/s00381-010-1241-8
• Authors
  • Constantin Roder, Department of Neurosurgery, University of Tubingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany
  • Vera Peters, Department of Neurosurgery, University of Tubingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany
  • Hidetoshi Kasuya, Division of Neurosurgery, Medical Center East, Tokyo Women's Medical University, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567 Japan
  • Tsutomu Nishizawa, Tokyo Women's Medical University and International Research and Educational Institute for Integrated Medical Sciences, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
  • Yayoi Takehara, Tokyo Women's Medical University and International Research and Educational Institute for Integrated Medical Sciences, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
  • Daniela Berg, Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases (DZNE), Hoppe-Seyler-Str. 3, 72076 Tubingen, Germany
  • Claudia Schulte, The Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tubingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany
  • Nadia Khan, Department of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine, 300 Pasteur Drive, Boswell Building, A301, Stanford, CA 94305-5327, USA
  • Marcos Tatagiba, Department of Neurosurgery, University of Tubingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany
  • Boris Krischek, Department of Neurosurgery, University of Tubingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany

• Journal Child’s Nervous System
• Online ISSN 1433-0350
• Print ISSN 0256-7040