Protein kinase Cη polymorphism and the susceptibilities to intracerebral hemorrhage in the Taiwan population

Protein kinase Cη (PRKCH) 1425G/A polymorphism has been suggested to be a susceptible genetic locus of stroke by genome-wide polymorphism analysis with several replication reports in the Asian populations. While this association was found to exist in the stroke subtype of lacunar infarction especially, the susceptibility of this genetic variant to the intracerebral hemorrhage (ICH) subtypes is unknown to date. This study examined the associations of PRKCH 1425G/A with ICH as well as the stratification of ICH subtypes in the Taiwan population. Genotyping was determined by PCR-based restriction and single strand conformation polymorphism for 381 controls and 303 ICH patients, including 266 deep ICH and 37 lobar ICH patients. Multivariable logistic regression was used to analyze the associations of PRKCH genotypes with stroke subtypes under dominant models. Covariables including age, sex, hypertension, diabetes mellitus, and total cholesterol level were analyzed to delineate the independency of associations. To account for the multiple testing, permutation testing of 1000 replicates was performed for empirical estimates. Distribution of the genotypes of PRKCH 1425G/A was similar while comparing controls (GG: 61%, GA: 33.3%, and AA: 5.7%) with the total ICH group (GG: 57.8%, GA: 36.6%, and AA: 5.6%, p=0.68) and the deep ICH group (GG: 60.2%, GA: 34.2%, and AA: 5.6%, p=0.99). Distribution differ between controls and lobar ICH (GG: 40.5%, GA: 54.1%, and AA: 5.4%, p=0.04). Multivariable logistic regression adjusting for age and sex showed a significant association of PRKCH 1425G/A with lobar ICH risks in a dominant model (OR = 2.4, 95% confidence interval (CI) 1.2 to 4.7, p=0.012). When additionally adjusting for hypertension and cholesterol level, this association remained significant (OR = 2.4, 95% CI 1.1 to 5.5, p=0.029). There was a borderline association of minor allele A with lobar ICH when compared with controls (OR = 1.73, 95% CI 1.01 to 2.9, p=0.039). The variation was not associated with deep ICH. In conclusion, PRKCH 1425G/A variant was not a risk locus for deep ICH phenotype. PRKCH 1425G/A to the susceptibility of lobar ICH shown in this report needs further replication.