Child's Nervous System

, Volume 27, Issue 2, pp 245–252 | Cite as

Common genetic polymorphisms in Moyamoya and atherosclerotic disease in Europeans

  • Constantin Roder
  • Vera Peters
  • Hidetoshi Kasuya
  • Tsutomu Nishizawa
  • Yayoi Takehara
  • Daniela Berg
  • Claudia Schulte
  • Nadia Khan
  • Marcos Tatagiba
  • Boris KrischekEmail author
Original Paper



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.


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.


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.


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.


Atherosclerotic disease Genetics Moyamoya disease Single nucleotide polymorphism 



This study was partly supported by a grant-in-aid for scientific research (C) from the grant Encouraging Development of Strategic Research Centers and Special Coordination Funds for Promoting Science and Technology both from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Conflicts of interest/disclosures



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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Constantin Roder
    • 1
  • Vera Peters
    • 1
  • Hidetoshi Kasuya
    • 2
  • Tsutomu Nishizawa
    • 3
  • Yayoi Takehara
    • 3
  • Daniela Berg
    • 4
  • Claudia Schulte
    • 5
  • Nadia Khan
    • 6
  • Marcos Tatagiba
    • 1
  • Boris Krischek
    • 1
    Email author
  1. 1.Department of NeurosurgeryUniversity of TübingenTübingenGermany
  2. 2.Division of Neurosurgery, Medical Center EastTokyo Women’s Medical UniversityTokyoJapan
  3. 3.Tokyo Women’s Medical University and International Research and Educational Institute for Integrated Medical SciencesTokyoJapan
  4. 4.Department of NeurodegenerationHertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases (DZNE)TübingenGermany
  5. 5.The Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative DiseasesUniversity of TübingenTübingenGermany
  6. 6.Department of Neurosurgery and Stanford Stroke CenterStanford University School of MedicineStanfordUSA

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