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

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.

Lysyl oxidase family gene polymorphisms and risk of aneurysmal subarachnoid hemorrhage: a case-control study

“…Our present study demonstrated that LOXL1 rs2165241 was associated with multiple IAs ruptures. This is different from our previous study, which did not find an association between LOXL1 and IAs susceptibility ( 14 ). This may be due to the fact that the pathobiology leading to IAs formation and its rupture are not exactly the same, causing the existing IA rupture (aSAH) is a separate process from an IA formation ( 12 ).…”

“…In the present study, significant associations between LOX (rs1800449 and rs10519694) and single IA rupture were detected. Similar to our previous study, it was found that LOX was associated with IA susceptibility (14), but these results are inconsistent with those of a previous study by Hong et al, who conducted a case-control study with 41 ruptured and 39 unruptured IA patients in a Korean population and showed that LOX may not be a susceptibility gene for IA rupture (17). We found that population heterogeneity may be the reason for the discordance between these 2 countries, and minor allele frequency in the 2 sites was discrepant between these 2 populations.…”

“…Using whole-exome sequencing, a significant association was also found with LOXL2 in FIA patients from a Chinese population (16). Our previous research also found that LOXL2 is associated with IA (14). Similarly, our present results also demonstrated that LOXL2 is associated with IA rupture but with multiple IAs, not total IA or single IA rupture.…”

“…Although numerous studies have explored the genetic susceptibility of aSAH, there are few studies on the association between LOX family gene polymorphisms and aSAH. Our previous study found that LOX was associated with the risk of single IA, while LOX-like 2 (LOXL2) was associated with the risk of multiple IAs (14). LOXL2, which belongs to the LOX family of genes, was found to be associated with susceptibility to familial IA (FIA) in Chinese and Japanese populations (15,16); In Korea, Hong et al discovered that LOX was associated with IA formation and rupture using candidate gene association analysis (17).…”

Molecular characteristics of arteries in patients with intracranial aneurysm: integration of WES and RNA-seq

“…Epidemiological investigations showed that rst-degree relatives of IA patients had 7 times higher risk for the disease than the general population [8]. Some large-sample case-control studies found that genetic variants of LOX, ANGPTL6, FBLN2, NOTCH3, PCNT, ARHGEF17 genes were associated with higher risks for IAs [9,10].…”