Common genetic polymorphisms in moyamoya and atherosclerotic disease in Europeans

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.