ABSTRACT
OBJECTIVE: Accumulated evidence suggests that a variant within the CR1 gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences ß-amyloid (Aß) deposition in brain tissue. Given the biologic overlap between AD and cerebral amyloid angiopathy (CAA), a leading cause of intracerebral hemorrhage (ICH) in elderly individuals, we investigated whether rs6656401 increases the risk of CAA-related ICH and influences vascular Aß deposition. METHODS: We performed a case-control genetic association study of 89 individuals with CAA-related ICH and 280 individuals with ICH unrelated to CAA and compared them with 324 ICH-free control subjects. We also investigated the effect of rs6656401 on risk of recurrent CAA-ICH in a prospective longitudinal cohort of ICH survivors. Finally, association with severity of histopathologic CAA was investigated in 544 autopsy specimens from 2 longitudinal studies of aging. RESULTS: rs6656401 was associated with CAA-ICH (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17, p = 8.0 × 10(-4)) as well as with risk of recurrent CAA-ICH (hazard ratio = 1.35, 95% CI 1.04-1.76, p = 0.024). Genotype at rs6656401 was also associated with severity of CAA pathology at autopsy (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Adjustment for parenchymal amyloid burden did not cancel this effect, suggesting that, despite the correlation between parenchymal and vascular amyloid pathology, CR1 acts independently on both processes, thus increasing risk of both AD and CAA. CONCLUSION: The CR1 variant rs6656401 influences risk and recurrence of CAA-ICH, as well as the severity of vascular amyloid deposition.
Subject(s)
Cerebral Amyloid Angiopathy/epidemiology , Cerebral Amyloid Angiopathy/genetics , Receptors, Complement 3b/genetics , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Apolipoproteins E/genetics , Autopsy , Confidence Intervals , Data Interpretation, Statistical , Female , Follow-Up Studies , Genetic Variation , Genome-Wide Association Study , Genotype , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk , Sex FactorsABSTRACT
OBJECTIVES: Vascular inflammation contributes to the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH). Interleukin 6 (IL6) is a proinflammatory cytokine involved in many vascular pathologies. Two studies analyzing an association of the functional IL6 gene -174G>C promoter polymorphism with aSAH provided inconsistent results. The aim of this study was to investigate whether this IL6 polymorphism is associated with aSAH in a Polish population. MATERIAL AND METHODS: We genotyped 276 aSAH patients and 581 unrelated control subjects. All were of Caucasian origin. In addition, a meta-analysis combining results of the current and previously published studies was conducted. RESULTS: The distribution of IL6 genotypes and alleles did not differ significantly between aSAH (GG - 29.7%, GC - 50.0%, CC - 20.2%, G - 54.7%) and control subjects (GG - 32.0%, GC - 47.3%, CC - 20.7%, G - 44.3%). In the meta-analysis, the IL6-174G>C polymorphism was not associated with aSAH risk either. CONCLUSIONS: We failed to find an association between the IL6 -174G>C polymorphism and aSAH in analyzed European populations.
Subject(s)
Interleukin-6/genetics , Polymorphism, Single Nucleotide/genetics , Subarachnoid Hemorrhage/genetics , Adult , Case-Control Studies , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Promoter Regions, Genetic/genetics , Risk Factors , White People/geneticsABSTRACT
BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with Alzheimer's disease (AD). However, their efficacy is moderate and differs from patient to patient. Recent studies suggest that the Q192R variant of the paraoxonase 1 gene (PON1) might affect individual susceptibility to these drugs. METHODS: We investigated the influence of 3 single nucleotide polymorphisms (SNPs) in PON1 (rs 662, rs 854560, rs 705381) and the APOE common polymorphism in 101 Polish patients with late-onset AD in response to treatment with AChEIs. RESULTS: No significant differences were observed between carriers and non-carriers of the PON1 SNPs or the APOE common polymorphism in terms of treatment response. These results did not change after stratification of APOE status. CONCLUSION: Our results suggest that both the investigated PON1 and APOE common SNPs do not influence treatment response to AChEIs in patients with AD.
