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

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease caused by intracranial aneurysm (IA) rupture. Lysyl oxidase (LOX) family genes (LOX-like [LOXL] 1-4) have roles in collagen cross-linking in the extracellular matrix (ECM) and may be associated with IA rupture. We aimed to explore the association between LOX polymorphisms and the risk of aSAH. METHODS: This case-control study included 2 cohorts: 133 single ruptured and 115 unruptured IA patients, and 65 multiple ruptured and 71 unruptured IA patients. Genotyping of 27 single nucleotide polymorphisms (SNPs) in LOX was performed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of the SNPs of LOX and the risk of aSAH. RESULTS: LOX rs1800449 and LOXL4 rs3793692 were positively associated with the risk of single IA rupture in the recessive model (OR =5.66, 2.06; 95% CI =1.22–26.24, 1.11–3.82, respectively) and LOX rs10519694 demonstrated a protective effect on single IA rupture (dominant model: OR =0.42, 95% CI =0.21–0.83; recessive model: OR =0.16, 95% CI =0.04–0.65; additive model: OR =0.46, 95% CI =0.28–0.78). LOXL1 rs2165241, LOXL2 rs1063582, and LOXL3 rs17010021 showed risk effects on multiple IAs rupture. LOXL3 rs17010022 showed a protective effect on multiple IAs ruptures (dominant model: OR =0.41, 95% CI =0.21–0.82; additive model: OR =0.51, 95% CI =0.30–0.85). CONCLUSIONS: LOX and LOXL4 may be susceptibility genes for single IA rupture, whereas LOXL1-3 may have a role in susceptibility to multiple IAs ruptures in the Chinese population, suggesting that LOX family genes may be associated with aSAH.