Polymorphisms in Lysyl Oxidase Family Genes Are Associated With Intracranial Aneurysm Susceptibility in a Chinese Population.

Junxia Yan,Dun Yuan,Chun Luo,Songlin Liu,Junyu Liu,Chongyu Hu,Yifeng Li,Lu Xu,Weixi Jiang,Jilin Zhou,Xin Liao,Liming Hu,Bingyang Li,Rui Dong

doi:10.3389/fendo.2021.642698

Abstract

PurposeIntracranial aneurysms (IA) comprise a multifactorial disease with unclear physiological mechanisms. The lysyl oxidase (LOX) family genes (LOX, LOX–like 1–4) plays important roles in extracellular matrix (ECM) reconstruction and has been investigated in terms of susceptibility to IA in a few populations. We aimed to determine whether polymorphisms in LOX family genes are associated with susceptibility to IA in a Chinese population.MethodsThis case-control study included 384 patients with IA and 384 healthy individuals without IA (controls). We genotyped 27 single nucleotide polymorphisms (SNPs) of LOX family genes using the Sequenom MassARRAY® platform. These SNPs were adjusted for known risk factors and then, odds ratios (OR) and 95% confidence intervals (CI) were evaluated using binary logistic regression analysis.ResultsThe result showed that LOX rs10519694 was associated with the risk of IA in recessive (OR, 3.88; 95% CI, 1.12–13.47) and additive (OR, 1.56; 95%CI, 1.05–2.34) models. Stratified analyses illustrated that LOX rs10519694 was associated with the risk of single IA in the recessive (OR, 3.95; 95%CI, 1.04–15.11) and additive (OR, 1.64; 95%CI, 1.04–2.56) models. The LOXL2 rs1010156 polymorphism was associated with multiple IA in the dominant model (OR, 1.92; 95%CI, 1.02–3.62). No associations were observed between SNPs of LOXL1, LOXL3, and LOXL4 and risk of IA.ConclusionLOX and LOXL2 polymorphisms were associated with risk of single IA and multiple IA in a Chinese population, suggesting potential roles of these genes in IA. The effects of these genes on IA require further investigation.

Highlights

Intracranial aneurysms (IA) are cystic bulges caused by local defects or increased pressure in the intracranial artery wall [1]
We found that the lysyl oxidase (LOX) rs10519694 and lysyl oxidase-like 2 (LOXL2) rs1010156 polymorphism was associated with the risk of single and multiple IA respectively
Similar to the findings of a case-control study by Hong et al, who associated the A allele of another polymorphism of LOX with decreased risk of IA (P = 8.2 × 10-4) in Korean population, we identified that this variant was associated with the decreased risk of single IA in Chinese, even a definite conclusion couldn’t be drawn considering the fact of that the statistical power was relatively low and the association was not replicated in the additional control

Summary

Introduction

Intracranial aneurysms (IA) are cystic bulges caused by local defects or increased pressure in the intracranial artery wall [1]. Unruptured intracranial aneurysms (UIA) occur in 3–5% of the global population and in 7% of Chinese persons aged 35–75 years [2,3,4,5]. The annual risk of IA rupture is 0.5–1.8% [6, 7]. The rupture of an IA can result in aneurysmal subarachnoid hemorrhage (aSAH), which can be fatal in 50% of patients and cause 33% of severe sequelae [8, 9]. Costs associated with aSAH supervision exceed £510 million annually in the UK [10]. Risk factors linked to IA should be determined as soon as possible to screen and treat IA more effectively

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