Byeong Ju Youn1,2, Hyun Sub Cheong3, Suhg Namgoong3, Lyoung Hyo Kim3, In Ki Baek1, Jeong-Hyun Kim4, Seon-Jin Yoon5,6, Eui Hyun Kim7, Se Hoon Kim8, Jong Hee Chang5, Sun Ho Kim5, Hyoung Doo Shin9,10,11. 1. Department of Life Science, Sogang University, 04107, Seoul, Republic of Korea. 2. Forensic DNA Division, National Forensic Service, 26460, Wonju, Republic of Korea. 3. Department of Genetic Epidemiology, SNP Genetics Inc, Seoul, Republic of Korea. 4. Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea. 5. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea. 6. Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea. 7. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea. EUIHYUNKIM@yuhs.ac. 8. Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea. 9. Department of Life Science, Sogang University, 04107, Seoul, Republic of Korea. hdshin@sogang.ac.kr. 10. Department of Genetic Epidemiology, SNP Genetics Inc, Seoul, Republic of Korea. hdshin@sogang.ac.kr. 11. Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea. hdshin@sogang.ac.kr.
Abstract
BACKGROUND: Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1. METHODS AND RESULTS: A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA. CONCLUSIONS: Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.
BACKGROUND: Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1. METHODS AND RESULTS: A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA. CONCLUSIONS: Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.
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