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Open Access 01-12-2017 | Research article

CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population

Authors: Yunchang Chen, Gancheng Li, Haiyan Fan, Shenquan Guo, Ran Li, Jian Yin, Xin Zhang, Xifeng Li, Xuying He, Chuanzhi Duan

Published in: BMC Neurology | Issue 1/2017

Abstract

Background

CDKN2BAS gene polymorphisms has been shown to correlation with intracranial aneurysm(IA) in the study of foreign people. The study, the author selected the Chinese people as the research object to explore whether CDKN2BAS gene polymorphisms associated with Chinese patients with IA.

Methods

We selected 200 patients(52.69 ± 11.50) with sporadic IA as experimental group, 200 participants(49.99 ± 13.00) over the same period to the hospital without cerebrovascular diseases as control group. Extraction of peripheral blood DNA, applying polymerase chain reaction(PCR)-ligase detection reaction (LDR) identified CDKN2BAS Single nucleotide polymorphism(SNP) locus genotype: rs6475606, rs1333040, rs10757272, rs3217992, rs974336, rs3217986, rs1063192. The differences in allelic and genotype frequencies between the patient and control groups were evaluated by the chi-square test or Fisher’s exact tests.

Results

The genotype of rs1333040 and rs6475606 shown association with sporadic IA(X² = 8.545, P = 0.014; X² = 10.961, P = 0.004; respectively);the C allele of rs6475606 showed reduction the occurrence of IA; the rs1333040 and rs6475606 associated with hemorrhage, the C allele of rs1333040 could lower the risk of hemorrhage, and rs6475606 will not, rs1333040 also associated with aneurysm size.

Conclusion

Our research shows that variant rs1333040 and rs6475606 of CDKN2BAS related to the Chinese han population of sporadic IAs occurs. This study confirms the association between CDKN2BAS and IAs.

Adeyemo A, Rotimi C. Genetic variants associated with complex human diseases show wide variation across multiple populations. Public Health Genomics. 2010;13(2):72–9. doi:10.1159/000218711.CrossRefPubMed

Bai Y, Nie S, Jiang G, Zhou Y, Zhou M, Zhao Y, et al. Regulation of CARD8 expression by ANRIL and association of CARD8 single nucleotide polymorphism rs2043211 (p.C10X) with ischemic stroke. Stroke. 2014;45(2):383–8. doi:10.1161/STROKEAHA.113.003393.CrossRefPubMedPubMedCentral

Bilguvar K, Yasuno K, Niemelä M, Ruigrok YM, von Und Zu Fraunberg M, van Duijn CM, et al. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008;40(12):1472–7. doi:10.1038/ng.240.CrossRefPubMedPubMedCentral

Bochenek G, Hasler R, El Mokhtari NE, Konig IR, Loos BG, Jepsen S, et al. The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10. Hum Mol Genet. 2013;22(22):4516–27. doi:10.1093/hmg/ddt299.CrossRefPubMed

Broadbent HM, Peden JF, Lorkowski S. Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRI locus on chromosome 9p. Hum Mol Genet. 2008;17(6):806–14.CrossRefPubMed

Foroud T, Koller DL, Lai D, Sauerbeck L, Anderson C, Ko N, et al. Genome-wide association study of intracranial aneurysms confirms role of Anril and SOX17 in disease risk. Stroke. 2012;43(11):2846–52. doi:10.1161/STROKEAHA.112.656397.CrossRefPubMedPubMedCentral

Foroud T, Lai D, Koller D, Van’t Hof F, Kurki MI, Anderson CS, et al. Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7. Stroke. 2014;45(11):3194–9. doi:10.1161/STROKEAHA.114.006096.CrossRefPubMedPubMedCentral

Hashikata H, Liu W, Inoue K, Mineharu Y, Yamada S, Nanayakkara S, et al. Confirmation of an Association of Single-Nucleotide Polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients. Stroke. 2010;41(6):1138–44. doi:10.1161/STROKEAHA.109.576694.CrossRefPubMed

Helgadottir A, Thorleifsson G, Magnusson KP, Grétarsdottir S, Steinthorsdottir V, Manolescu A, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40(2):217–24.CrossRefPubMed

10.

Holdt LM, Teupser D. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol. 2012;32(2):196–206. doi:10.1161/ATVBAHA.111.232678.CrossRefPubMed

11.

Hunter DJ. Gene–environment interactions in human diseases. Nat Rev Genet. 2005;6(2):287–98.CrossRefPubMed

12.

Koichi Akiyama ANHN, Atsushi Tajima BKKY. Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms. J Hum Genet. 2010;55(10):656–61. doi:10.1038/jhg.2010.82.CrossRefPubMed

13.

Low SK, Takahashi A, Cha PC, Zembutsu H, Kamatani N, Kubo M, et al. Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA. Hum Mol Genet. 2012;21(9):2102–10. doi:10.1093/hmg/dds020.CrossRefPubMed

14.

Nie FQ, Sun M, Yang JS, Xie M, Xu TP, Xia R, et al. Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther. 2015;14(1):268–77. doi:10.1158/1535-7163.MCT-14-0492.CrossRefPubMed

15.

Pan W, Liu L, Wei J, Ge Y, Zhang J, Chen H, et al. A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol Carcinog. 2016;55(1):90–6. doi:10.1002/mc.22261.CrossRefPubMed

16.

Pasmant E, Sabbagh A, Vidaud M, Bieche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 2011;25(2):444–8. doi:10.1096/fj.10-172452.CrossRefPubMed

17.

Ruigrok YM, Rinkel GJ. From GWAS to the clinic: risk factors for intracranial aneurysms. Genome Med. 2010;2(9):61. doi:10.1186/gm182.CrossRefPubMedPubMedCentral

18.

Suo M, Lin Y, Yu H, Song W, Sun K, Song Y, et al. Association of Kallikrein gene polymorphisms with sporadic intracranial aneurysms in the Chinese population. J Neurosurg. 2014;120(6):1397–401. doi:10.3171/2013.11.JNS131036.CrossRefPubMed

19.

Wu SC, Kallin EM, Zhang Y. Role of H3K27 methylation in the regulation of lncRNA expression. Cell Res. 2010;20(10):1109–16. doi:10.1038/cr.2010.114.CrossRefPubMedPubMedCentral

20.

Yasuno K, Bakircioglu M, Low SK, Bilguvar K, Gaal E, Ruigrok YM, et al. Common variant near the endothelin receptor type a (EDNRA) gene is associated with intracranial aneurysm risk. Proc Natl Acad Sci. 2011;108(49):19707–12. doi:10.1073/pnas.1117137108.CrossRefPubMedPubMedCentral

21.

Yasuno K, Bilguvar K, Bijlenga P, Low S, Krischek B, Auburger G, et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nat Genet. 2010;42(5):420–5. doi:10.1038/ng.563.CrossRefPubMedPubMedCentral

22.

Ynte M, Ruigrok GJER. Genetics of intracranial aneurysms. Lancet Neurol. 2005;4(1):179–87.

23.

Zhu Y, Li W, Ge M, Xu S, Zhao G, Wang H, et al. Polymorphism rs42524 of COL1A2 and sporadic intracranial aneurysms in the Chinese population. J Neurosurg. 2008;109(6):1060–4. doi:10.3171/JNS.2008.109.12.1060.CrossRefPubMed

Title: CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population
Authors: Yunchang Chen
Gancheng Li
Haiyan Fan
Shenquan Guo
Ran Li
Jian Yin
Xin Zhang
Xifeng Li
Xuying He
Chuanzhi Duan
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-017-0986-z

At a glance: The STEP trials

Springer Medicine

CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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