Association of the Jun dimerization protein 2 gene with intracranial aneurysms in Japanese and Korean cohorts as compared to a Dutch cohort

• Published in: Neuroscience Vol. 169; no. 1; pp. 339 - 343
• Main Authors: Krischek, B, Tajima, A, Akagawa, H, Narita, A, Ruigrok, Y, Rinkel, G, Wijmenga, C, Feigl, G.C, Kim, C.J, Hori, T, Tatagiba, M, Kasuya, H, Inoue, I
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 11.08.2010; Elsevier
• Subjects: Aged; Alleles; Aneurysm; Asian Continental Ancestry Group - genetics; Biological and medical sciences; candidate gene; Cohort Studies; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Humans; intracranial aneurysm; Intracranial Aneurysm - ethnology; Intracranial Aneurysm - genetics; Introns - genetics; Japan - epidemiology; Jun dimerization protein 2; Korea - epidemiology; Male; Middle Aged; Netherlands - epidemiology; Neurology; Polymorphism, Single Nucleotide; Protein Isoforms - genetics; Repressor Proteins - genetics; Repressor Proteins - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; single nucleotide polymorphism; Untranslated Regions - genetics; Vertebrates: nervous system and sense organs; Netherlands; Japan; Korea; c-Jun N-terminal kinase; single nucleotide polymorphism; JNK; MMPs; basic leucine zipper transcription factor; AP-1; BATF; candidate gene; activator protein 1; intracranial aneurysm; SNP; IA; Jun dimerization protein 2; single nucleotide polymorphisms; matrix metalloproteinases; JDP2; Protein; Polymorphism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.05.002

Abstract In a previous study a linkage region for association to IA patients was found on chromosome 14q22. In this study, we report the findings of a positional candidate gene, Jun dimerization Protein 2 ( JDP2 ), and single nucleotide polymorphisms (SNP) of that gene that are associated with intracranial aneurysms in different ethnic populations. We screened the linkage region around chromosome 14q22 and narrowed it down to JDP2 . We then genotyped case and control groups of three different ethnic populations: 403 Japanese intracranial aneurysm (IA) cases and 412 controls, 181 Korean IA cases and 181 controls, 379 Dutch cases and 642 Dutch controls. Genotyping was performed using polymerase chain reaction and direct sequencing technology. The allele distribution of three SNPs (two intronic: rs741846; P =0.0041 and rs175646; P =0.0014, and one in the untranslated region: rs8215; P =0.019) and their genotype distribution showed significant association in the Japanese IA patients. The allelic and genotypic frequency of one intronic SNP (rs175646; P =0.0135 and P =0.0137, respectively) and the genotypic frequency for the SNP in the UTR region (rs8215; P =0.049) was also significantly different between cases and controls of the Korean cohort. There was no difference in allelic or genotypic frequencies in the Dutch population. These SNPs in JDP2 are associated with intracranial aneurysms, suggesting that variation in or near JDP2 play a role in susceptibility to IAs in East Asian populations.