Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec;29(8):769-76.
doi: 10.1177/1533317514539541. Epub 2014 Jun 24.

Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer's disease and vascular dementia

Rizwan Alam  1 , Manjari Tripathi  2 , Nasim Mansoori  3 , Shama Parveen  4 , Kalpana Luthra  5 , Ramakrishnan Lakshmy  6 , Subhadra Sharma  3 , Subramanian Arulselvi  7 , Asok K Mukhopadhyay  8
Affiliations

Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer's disease and vascular dementia

Rizwan Alam et al. Am J Alzheimers Dis Other Demen. 2014 Dec.

Abstract

Genetic polymorphism and epistasis play a role in etiopathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). In this case-control study, a total of 241 patients were included in the study to see the effect of paraoxonase 1 (PON1; rs662 and rs85460) and apolipoprotein E (ApoE) genes in altering the odds of having AD and VaD along with serum PON and lipid profile. The presence of at least 1 variant allele of rs662, but not rs85460, increased the risk of having AD by 1.8-fold (95% confidence interval [CI]: 0.97-3.40) and VaD by 3.09-fold (95% CI: 1.4-6.9). The interaction between PON1 genes (rs662 and rs85460) and ApoE genes showed synergistic epistasis in altering the odds of significantly having both AD and VaD. On the other hand, low serum level of high-density lipoprotein and low level of serum PON activity were found associated significantly (P ≤ .001 in both cases) only in patients with VaD as compared to healthy control.

Keywords: Alzheimer’s disease; apolipoprotein; lipid profile; paraoxonase; synergistic epistasis; vascular dementia.

PubMed Disclaimer

Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Comment in

References

    1. Combarros O, Cortina-Borja M, Smith AD, Lehmann DJ. Epistasis in sporadic Alzheimer’s disease. Neurobiol Aging. 2009;30 (9):1333–1349. - PubMed
    1. Rosenblat M, Karry R, Aviram M. Paraoxonase 1 (PON1) is a more potent antioxidant and stimulant of macrophage cholesterol efflux, when present in HDL than in lipoprotein-deficient serum: relevance to diabetes. Atherosclerosis. 2006;187 (1):74–81. - PubMed
    1. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989; 320 (14):915–924. - PubMed
    1. Holvoet P, Peeters K, Lund-Katz S, et al. . Arg123-Tyr166 domain of human ApoA-I is critical for HDL-mediated inhibition of macrophage homing and early atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2001;21 (12):1977–1983. - PubMed
    1. Parthasarathy S, Wieland E, Steinberg D. A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1989;86 (3):1046–1050. - PMC - PubMed

Publication types