Yonsei Med J.  2017 Sep;58(5):1006-1011. 10.3349/ymj.2017.58.5.1006.

A Novel Association between Lysyl Oxidase Gene Polymorphism and Intracranial Aneurysm in Koreans

• Hong EP
• Jeon JP
• Kim SE
• Yang JS
• Choi HJ
• Kang SH
• Cho YJ

• KMID: 2418938
• DOI: http://doi.org/10.3349/ymj.2017.58.5.1006

Abstract

PURPOSE
Lysyl oxidase (LOX) controls the cross-linking and maturation of elastin and collagen fibers. In this study, we investigated the association between LOX gene polymorphisms and intracranial aneurysm (IA) formation in a homogeneous Korean population.
MATERIALS AND METHODS
This cross-sectional study involved 80 age-sex matched patients with IA and controls. Fisher's exact test was performed to analyze allelic associations between ten single nucleotide polymorphisms (SNPs) and IA, including 41 ruptured and 39 unruptured cases. Haplotype-specific associations were analyzed using the omnibus test estimating asymptotic chi-square statistics.
RESULTS
Of ten SNPs, three SNPs (rs2303656, rs3900446, and rs763497) were significantly associated with IA (p<0.01). The C allele of rs3900446 was significantly related to increased IA risk with a significant threshold [odds ratio (OR)=20.15, p=4.8×10⁻⁵]. Meanwhile, the A allele of rs2303656 showed a preventive effect against IA formation (p=8.2×10⁻⁴). Seventeen of 247 haplotype structures showed a suggestive association with IA (asymptotic p<0.001). Of ten SNP haplotype combinations, the CG combination of rs3900446 and rs763497 reached Bonferroni-adjusted significant threshold in IA patients (minor haplotype frequency=0.113, asymptotic p=1.3×10⁻⁵). However, there was no association between aneurysm rupture and the LOX gene.
CONCLUSION
This preliminary study indicated that LOX gene polymorphisms, such as rs2303656, rs3900446, and rs763497, may play crucial roles in IA formation in the Korean population. Our novel findings need to be validated in a large-scale independent population.

Keyword

Intracranial aneurysm; subarachnoid hemorrhage; lysyl oxidase; SNP

MeSH Terms

Asian Continental Ancestry Group/*genetics
Case-Control Studies
Demography
Female
*Genetic Predisposition to Disease
Haplotypes/genetics
Humans
Intracranial Aneurysm/*enzymology/*genetics
Linkage Disequilibrium/genetics
Male
Middle Aged
Polymorphism, Single Nucleotide/*genetics
Protein-Lysine 6-Oxidase/*genetics
Protein-Lysine 6-Oxidase

Figure

• 

  Fig. 1 Linkage disequilibrium patterns of 10 Lysyl oxidase SNPs in patients with intracranial aneurysm (A), controls (B), and total groups (C). SNPs, single nucleotide polymorphisms.

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