Gene–Environment Interaction in Alzheimer’s Disease

Singh, Neeraj; Chhillar, Neelam; Banerjee, Basu Dev; Bala, Kiran; Mukherjee, Amit; Mustafa, Muhammad; Mitrabasu,

doi:10.1177/1533317512456067

Cited by 23 publications

(20 citation statements)

References 37 publications

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“…The present study showed high frequency of ε4 allele in AD, which is in accordance with other findings (Thelma et al, 2001;Kapur et al, 2006;singh et al, 2012). The precise mechanisms by which APOE isoforms and lipids are involved in the pathogenesis of AD still remain unclear.…”

Section: Discussionsupporting

confidence: 93%

“…The specific primers 5'-ACAGAATTCGCCCCGGCCTGGTAC-AC-3' and 5'-TAAGCTTGGCACGGCTGTCC AAGGA-3' were used for amplification (Singh et al, 2012). PCR assay was performed on Bio-Rad iQ5 cycler, USA, in a 20µl volume of 1x high-fidelity master mix (Bio-Rad) containing high-fidelity buffer, 0.04U/µl DNA polymerase, 1.5mM MgCl2, 200µM dNTPs.…”

Section: Apoe Genotypingmentioning

confidence: 99%

“…The OCPs α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, Aldrin, Dieldrin, α-endosulfan, β-endosulfan, pp'-Dichlorodiphenyldichloroethylene (pp'-DDE), op'-DDE, pp'-Dichlorodiphenyl-trichloroethane (pp'-DDT), op '-DDT, pp'-Dichlorodiphenyldichloro-ethane (pp'-DDD) and op'-DDD were assayed. The compounds selected for assay were based on previous findings (Singh et al, 2012;Singh et al, 2013) that indicated the pesticides most commonly found in human samples and based on the compounds assayed by the Environmental Protection Agency. Samples were analysed on Perkin Elmer Gas Chromatograph equipped with 63Ni electron capture detector under standard operating procedure (Singh et al, 2012;Singh et al, 2013).…”

Section: Estimation Of Organochlorine Pesticidesmentioning

confidence: 99%

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β-hexachlorocyclohexane as a Risk for Alzheimer’s Disease: A Pilot Study in North Indian Population

Chhillar¹,

Singh²,

Banerjee³

et al. 2013

AJAD

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The notion of potential existence of gene environment interaction (GxE) in Alzheimer's disease (AD) has substantial impact on understanding the role of genetic and non-genetic contribution to this disorder. Keeping in mind this background we examined the genetic and environmental factors which may determine their relative contribution to AD. Based on well defined inclusion and exclusion criteria this study includes 70 AD patients and 75 age-matched controls. Organochlorine Pesticides (OCPs) were analyzed in blood by using gas chromatography and serum metals were analyzed by using an autoanalyser. The LRPAP1 and APOE gene polymorphism were determined by polymerase chain reaction and restriction fragment length polymorphism respectively. The frequency of APOE ε4 allele and LRPAP1 I allele were significantly high (p=0.000 for both allele) in AD patients as compared to controls. The significantly high levels of β-hexachlorocyclohexane (β-HCH) and dieldrin are risk factors for AD independent of the genetic risk factor, recording an odds ratio of 2.777 and 2.344 respectively. This study suggests that out of the environmental factors, high β-HCH levels were the best predictor of presence of AD independent of the genetic component and low levels of serum iron play a protective role against AD.

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Section: Discussionsupporting

confidence: 93%

Section: Apoe Genotypingmentioning

confidence: 99%

Section: Estimation Of Organochlorine Pesticidesmentioning

confidence: 99%

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β-hexachlorocyclohexane as a Risk for Alzheimer’s Disease: A Pilot Study in North Indian Population

Chhillar¹,

Singh²,

Banerjee³

et al. 2013

AJAD

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“…Extraction of OCP residues was done by using HPLC- grade hexane and acetone (2 : 1) according to method of Singh et al [11]. Hexane (6 mL) and acetone (3 mL) were added and the contents were shaken at room temperature for 30 minutes in a mechanical shaker.…”

Section: Methodsmentioning

confidence: 99%

“…The remaining portion was again extracted twice using the same process and the hexane fractions were added to the previous solvent fractions. Cleanup was done by USEPA method by column chromatography as described by Singh et al [11]. Florisil was activated at 130°C overnight and cooled in a dessicator before use.…”

Section: Methodsmentioning

confidence: 99%

Organochlorine Pesticide Levels and Risk of Parkinson’s Disease in North Indian Population

et al. 2013

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The cause of Parkinson's disease (PD) remains elusive, but environmental chemical exposures have been postulated to be involved in the etiology of PD. We examined the association between the persistent organochlorine pesticides (OCPs) and PD in the North Indian population. This case control study included 70 PD and 75 control subjects in the age group of 50 to 85 years. Blood samples were collected and high-purity grade hexane and acetone (2 : 1 ratio) were used for extraction of organochlorine residues. OCPs (hexachlorocyclohexane (HCH), aldrin, dieldrin, endosulfan, pp′-Dichlorodiphenyldichloroethylene (pp′-DDE), op′-DDE, pp′- Dichlorodiphenyltrichloroethane (pp′-DDT), op′-DDT, pp′-dichlorodiphenyldichloroethane (pp′-DDD) and op′-DDD) were quantitatively estimated by using gas chromatography. The most frequently detected OCP was dieldrin, which was present in 9.3% of control and 61.4% of PD. The strongest predictor was β-hexachlorocyclohexane (β-HCH), which reported an odds ratio of 2.566, indicating that for every additional one unit of β-HCH, patients had 2.566 times more chances of presence of PD. This study indicates that increased level of β-HCH and dieldrin may be associated with the risk of PD.

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APOE and LRPAP1 gene polymorphism and risk of Parkinson’s disease

et al. 2014

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Epidemiologic findings suggest that lipids and alteration in lipid metabolizing protein/gene may contribute to the development of neurodegenerative disorders. The aim of the current study was to determine the serum lipid levels and genetic variation in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein (LRPAP1) and apolipoprotein E (APOE) gene in Parkinson's disease (PD). Based on well-defined inclusion and exclusion criteria, this study included 70 patients with PD and 100 age-matched controls. LRPAP1 and APOE gene polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism, respectively. Fasting serum lipid levels were determined using an autoanalyser. The logistic regression analysis showed that high levels of serum cholesterol [odds ratio (OR) = 1.101, 95 % confidence interval (CI95%) = 1.067-1.135], LRPAP1 I allelic variant alone (OR = 2.766, CI95% = 1.137-6.752) and in combination with APOE ε4 allelic variant (OR = 4.187, CI95% = 1.621-10.82) were significantly associated with increase in PD risk. Apart from that, the high levels of LDL cholesterol appears to have a protective role (OR = 0.931, CI95% = 0.897-0.966) against PD. The LRPAP1 I allelic variant may be considered a candidate gene for PD, predominantly in patients having the APOE ε4 allelic variant.

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Gene–Environment Interaction in Alzheimer’s Disease

Abstract: GxE interactions exist with APOE ∈4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.

Cited by 23 publications

References 37 publications

β-hexachlorocyclohexane as a Risk for Alzheimer’s Disease: A Pilot Study in North Indian Population

β-hexachlorocyclohexane as a Risk for Alzheimer’s Disease: A Pilot Study in North Indian Population

Organochlorine Pesticide Levels and Risk of Parkinson’s Disease in North Indian Population

APOE and LRPAP1 gene polymorphism and risk of Parkinson’s disease

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