title: Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer's disease and vascular dementia.
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.
authors: Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
authors: Rizwan
authors: R
authors: Alam
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors: Manjari
authors: M
authors: Tripathi
authors: Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors: Nasim
authors: N
authors: Mansoori
authors: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
authors: Shama
authors: S
authors: Parveen
authors: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors: Kalpana
authors: K
authors: Luthra
authors: Department of Cardiac biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors: Ramakrishnan
authors: R
authors: Lakshmy
authors: Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors: Subhadra
authors: S
authors: Sharma
authors: JPN Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India.
authors: Subramanian
authors: S
authors: Arulselvi
authors: Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India mukhoak1953@gmail.com.
authors: Asok K
authors: AK
authors: Mukhopadhyay
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015140:Dementia, Vascular / Q000097:blood / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D053327:Apolipoprotein E4; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Alzheimer’s disease; apolipoprotein; lipid profile; paraoxonase; synergistic epistasis; vascular dementia