Lysyl oxidase family genes polymorphisms and risk of aneurysmal subarachnoid hemorrhage: A case control study

Introduction: 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 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 two cohorts: 133 and 115 single ruptured and unruptured IA patients, and 65 and 71 multiple ruptured and unruptured IAs patients, respectively. Genotyping of 27 single nucleotide polymorphisms (SNPs) in LOX was performed. Logistic regression analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) of the SNPs of LOX and risk of aSAH. Results LOX rs180044 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 demonstrated risk effects on multiple IAs rupture. LOXL3 rs17010022 showed a protective effect on multiple IAs rupture (dominant model: OR = 0.41, 95% CI = 0.21–0.82; additive model: OR = 0.51, 95% CI = 0.30–0.85). Discussion LOX and LOXL4 may be susceptible to single IA rupture, whereas LOXL1-3 may have a role in susceptibility to multiple IAs rupture in the Chinese population, suggesting LOX family genes may associated with aSAH.