Background: Pathway analysis demonstrated associations between deep intracerebral hemorrhage (DICH) and the genetic risk score of complex IV of the oxidative phosphorylation (OXPHOS) pathway in whites. This study investigated the related genetic variations in the DICH population in Taiwan. Candidate variants were selected from the prior report by the following criteria: (1) nuclear genes encoding mitochondria complex IV, (2) genetic effect >1.08, (3) global minor allele frequency >0.01. Six single-nucleotide polymorphisms fitted in the selection criteria, which were mainly involved in Cox assembly, including Cox10, Cox15, and Cox18, and one structural gene, Cox7C. Associations were tested with adjustment of multiple covariables. Permutation testing of 1000 replicates was performed for empirical estimates.
Results: This study enrolled 336 patients and 379 controls. Compared with whites, the Taiwan population has higher minor allele frequency (MAF) of rs4308511, rs767844, and rs221592 and lower MAF of rs8079640. There was no variation of rs16949067 in the Taiwan population. When adjusting for the traditional risk factors, rs221592 G allele was associated with DICH risk in women under additive (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.02-2.3, P = .04) and recessive models (OR = 2.9, 95% CI = 1.2-6.9, P = .013). In an additive fashion, a poor 30-day outcome was associated with rs4308511 T allele (OR = 1.6, 95% CI = 1.1-2.3, P = .014) and rs9891372 C allele (OR = 1.7, 95% CI = 1.05-2.8, P = .024) in all subjects and in men (rs4308511, OR = 1.8, 95% CI = 1.2-2.7, P = .008; rs9891372, OR = 2.1, 95% CI = 1.1-3.8, P = .02).
Conclusions: The results showed ethnic disparities in the complex IV-related genes. COX18-rs221592 G allele was associated with female DICH risks. COX7C-rs4308511 T allele was an independent risk of poor outcome in men.
Keywords: Intracerebral hemorrhage; association study; oxidative phosphorylation; polymorphism; stroke.