Codon 311 (Cys → Ser) polymorphism of paraoxonase-2 gene is associated with apolipoprotein E4 allele in both Alzheimer's and vascular dementias

Abstract

The gene of an esterase enzyme, called paraoxonase (PON, EC.3.1.8.1.) is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7. 1,2 The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction. 3-8 The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD) 9-13 prompted us to examine the genetic effect of PON2 gene codon 311 (Cys→Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD.

Integrative analysis of multi-dimensional imaging genomics data for Alzheimer's disease prediction

“…For example, the most top selected SNPs in HGM-FS method in multiclass classifications come from gene “CTNNA3,” which is a protein-coding gene and is associated to late-onset Alzheimer's disease (Miyashita et al, 2007 ). The most top selected SNPs in SMML method in multiclass classifications come from gene “PON2,” which encodes paraoxonase-2 gene and is associated with apolipoprotein E4 allele in both Alzheimer's and vascular dementias (Janka et al, 2001 ). The most top selected SNPs in MKL method in multiclass classifications also come from gene “CTNNA3” and gene “PON2.” Although the well-known APOE SNP is not the top one SNP in our list, it still appears in the top rank list.…”

Age-related macular degeneration a new viewpoint

“…Although the APOE epsilon 2 displayed an increased risk for AMD, it did not approach statistical significance. The APOE epsilon 4 association with AMD is intriguing, since it is known to be a strong risk factor for Alzheimers disease (36,41,89), also a disease of old age.…”

DJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress

“…PON2 deficiency in mice increases the risk of oxidative stress-related pathophysiological conditions such as development of atherosclerotic lesions [27], [28]. Furthermore, numerous studies on several human populations reported the association of PON2 polymorphisms with severe ischemic stroke [32], sporadic amyotrophic lateral sclerosis (SALS) [33], [34], [35], asthma [36] and Alzheimer's disease (AD) [37], [38]. Polymorphisms in another PON member, PON1, have also been associated with susceptibility to PD [39], [40].…”