Association Studies of Specific Cholesterol Related Genes (APOE,LPL,and CETP) with Lipid Profile and Memory Function: A Correlative Study Among Rural and Tribal Population of Dharmapuri District,India
Restricted accessResearch articleFirst published online September 15, 2017
Association Studies of Specific Cholesterol Related Genes (APOE,LPL,and CETP) with Lipid Profile and Memory Function: A Correlative Study Among Rural and Tribal Population of Dharmapuri District,India
Epidemiological studies state that dementia has multiple etiologies including genetic mutation, genetic variation, and environmental factors. Accumulating evidence suggests that dysregulation of cholesterol homeostasis is the major etiological factor in initiating neurodegeneration. Apolipoprotein E (APOE) polymorphic alleles and associated polymorphism of lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) that are important components in regulating cholesterol metabolism are implicated in neurodegenerative diseases. Therefore, the current study focused on identifying the association between several common polymorphism (viz., APOE, CETP, and LPL) to that of change in serum lipid levels and memory symptoms. Volunteer subjects aged 50 and above from rural and tribal areas of the Dharmapuri district, Tamilnadu, India were chosen for the current study and polymorphism was analyzed using PCR-RFLP. Fasting lipid profile and memory function using simplified version of Global Clinical Dementia rating were assessed. Significant difference in the major lipid profile parameters were observed (TC, TGL, LDL, VLDL) among rural and tribal populations that were associated with significant genotypic variation of APOE, CETP, and LPL. Regression analysis revealed significant risk for memory loss that are dependent on age and genetic variants like CETP. These data predict positive correlation between cholesterol-associated genes and their relationship to altered lipid profile and memory symptoms, which possibly link gene-polymorphism and susceptibility ratio for aging and dementia.
ShankarSK (2010) Biology of aging brain. Indian J Pathol Microbiol53, 595–604.
3.
ShajiS, BoseS, VergheseA (2005) Prevalence of dementia in an urban population in Kerala, India. Br J Psychiatry186, 136–140.
4.
BitraVR, RapakaD, AkulaA (2015) Prediabetes and Alzheimer’s disease. Indian J Pharm Sci77, 511–514.
5.
KulminskiA, UkraintsevaSV, ArbeevKG, MantonKG, OshimaJ, MartinGM, YashinAI (2008) Association between APOE epsilon 2/epsilon 3/ epsilon 4 polymorphism and disability severity in a national long-term care survey sample. Age Ageing37, 288–293.
6.
MartinsIJ, BergerT, SharmanMJ, VerdileG, FullerSJ, MartinsRN (2009) Cholesterol metabolism and transport in the pathogenesis of Alzheimer’s disease. J Neurochem111, 1275–1308.
7.
BaumL, ChenL, MasliahE, ChanYS, NgHK, PangCP (1999) Lipoprotein lipase mutations and Alzheimer’s disease. Am J Med Genet88, 136–139.
8.
ParadisE, ClavelS, JulienP, MurthyMR, de BilbaoF, ArsenijevicD, GiannakopoulosP, ValletP, RichardD (2004) Lipoprotein lipase and endothelial lipase expression in mouse brain: Regional distribution and selective induction following kainic acid induced lesion and focal cerebral ischemia. Neurobiol Dis15, 312–325.
SathyaM, MoorthiP, PremkumarP, KandasamyM, JayachandranKS, AnusuyadeviM (2016) Resveratrol intervenes in the cholesterol- and isoprenoid-mediated amyloidogenic processing of AβPP in familial Alzheimer’s disease. J Alzheimers Dis, doi: 10.3233/JAD-161034
11.
JhooJH, KimKW, SuhYJ, LeeDY, YounJC, LeeJH, WooJI (2004) The gender-and age dependency of the risk for Alzheimer’s disease conferred to apolipoprotein E polymorphism in Koreans. Psychiatry Invest1, 56–60.
12.
ChenXF, WeiZ, WangT, ZhangZL, WangY, HeckmanMG, DiehlNN, ZhangYW, XuH, BuG (2015) Demographic and lifestyle characteristics, but not apolipoprotein E genotype, are associated with intelligence among young Chinese college students. PLos One10, e0143157.
13.
FarrerLA, CupplesLA, HainesJL, HymanB, KukullWA, MayeuxR, MyersRH, Pericak-VanceMA, RischN, van DuijnCM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta-Analysis Consortium. JAMA278, 1349–1356.
14.
GoldmanJS, HahnSE, CataniaJW, Larusse-EckertS, ButsonMB, RumbaughM, StreckerMN, RobertsJS, BurkeW, MayeuxR, BirdT, American College of Medical Genetics and the National Society of Genetic Counselors (2011) Genetic counselling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med13, 597–605.
15.
BertramL (2009) Alzheimer’s disease genetics current status and future perspectives. Int Rev Neurobiol84, 167–184.
16.
AltmannA, TianL, HendersonVW, GreiciusMD, Alzheimer’s Disease Neuroimaging Initiative Investigators
(2014) Sex modifies the APOE-related risk of developing Alzheimer’s disease. Ann Neurol75, 563–573.
17.
MahleyRW (2016) Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Arterioscler Thromb Vasc Biol36, 1305–1315.
18.
BaumL, WiebuschH, PangCP (2000) Roles for lipoprotein lipase in Alzheimer’s disease: An association study. Microsc Res Tech50, 291–296.
19.
BarterPJ, KasteleinJJ (2006) Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol47, 492–499.
20.
HottmanDA, ChernickD, ChengS, WangZ, LiL (2014) HDL and cognition in neurodegenerative disorders. Neurobiol Dis72, 22–36.
21.
YuL, ShulmanJM, ChibnikL, LeurgansS, SchneiderJA, De JagerPL, BennettDA (2012) The CETP I405V polymorphism is associated with an increased risk of Alzheimer’s disease. Aging Cell11, 228–233.
22.
AliH, JafarS, Qurat-ul-Ain (2016) Optimized genomic DNA extraction by a modified organic phenol-chloroform method without using PCR for best results. Int J Res Med Sci4, 100–104.
23.
YinR, PanS, WuJ, LinW, YangD (2008) Apolipoprotein E gene polymorphism and serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. Exp Biol Med (Maywood)233, 409–418.
24.
PanSL, WangF, LuZP, LiuCW, HuCY, LuoH, PengJH, LuoXQ, PangGF, LuSH, WuHY, HuangLJ, YinRX (2012) Cholesteryl ester transfer protein TaqIB polymorphism and its association with serum lipid levels and longevity in Chinese Bama Zhuang population. Lipids Health Dis11, 26.
25.
CorellaD, SáizC, GuillénM, PortolésO, MuletF, GonzálezJI, OrdovásJM (2000) Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population. Atherosclerosis152, 367–376.
26.
XiaoZ, WangJ, ChenW, WangP, ZengH, ChenW (2012) Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease. Lipids Health Dis11, 163.
27.
McKhannG, DrachmanD, FolsteinM, KatzmanR, PriceD, StadlanEM (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology34, 939–944.
28.
SayadA, NoruziniaM, ZamaniM, HarirchianMH, KazemnejadA (2012) Lipoprotein lipase HindIII intronic polymorphism in a subset of Iranian patients with late-onset Alzheimer’s disease. Cell J14, 67–72.
29.
DixitM, BhattacharyaS, MittalB (2005) Association of CETP TaqI and APOE polymorphisms with type II diabetes mellitus in North Indians: A case control study. BMC Endocr Disord5, 7.
30.
ChoYS, GoMJ, HanHR, ChaSH, KimHT, MinH, ShinHD, ParkC, HanBG, ChoNH, ShinC, KimmK, OhB (2008) Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus. Exp Mol Med40, 523–532.
31.
WangH, EckelRH (2012) Lipoprotein lipase in the brain and nervous system. Annu Rev Nutr32, 147–160.
32.
NiculescuLS, TomaL, IanasO, SimaAV (2012) Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment. Cent Eur J Biol7, 419–430.
33.
BlainJF, AumontN, ThérouxL, DeaD, PoirierJ (2006) A polymorphism in lipoprotein lipase affects the severity of Alzheimer’s disease pathophysiology. Eur J Neurosci24, 1245–1251.
34.
Arias-VásquezA, IsaacsA, AulchenkoYS, HofmanA, OostraBA, BretelerM, Van DuijnCM (2007) The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer’s disease. Neurogenetics8, 189–193.
35.
KnouffC, HinsdaleME, MezdourH, AltenburgMK, WatanabeM, QuarfordtSH, SullivanPM, MaedaN (1999) Apo E structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest103, 1579–1586.
36.
MunshiA, BabuMS, KaulS, RajeshwarK, BalakrishnaN, JyothyA (2012) Association of LPL gene variant and LDL, HDL, VLDL cholesterol and triglyceride levels with ischemic stroke and its subtypes. J Neurol Sc318, 51–54.
37.
GalatiF, ColonnaP, GalatiA, CiardielloC, BozzettiMP, MassariS (2014) CETP TaqIB polymorphism, serum lipid levels and risk of atrial fibrillation: A case-control study. J Atr Fibrillation6, 964.
38.
KuoYM, EmmerlingMR, BisgaierCL, EssenburgAD, LampertHC, DrummD, RoherAE (1998) Elevated low-density lipoprotein in Alzheimer’s disease correlates with brain abeta 1-42 levels. Biochem Biophys Res Commun252, 711–715.
39.
MerchedA, XiaY, VisvikisS, SerotJM, SiestG (2000) Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer’s disease. Neurobiol Aging21, 27–30.
40.
PaniA, MandasA, DiazG, AbeteC, CoccoPL, AngiusF, BrunduA, MuçakaN, PaisME, SabaA, BarberiniL (2009) Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease. BMC Med7, 66.
41.
HallK, MurrellJ, OgunniyiA, DeegM, BaiyewuO, GaoS, GurejeO, DickensJ, EvansR, Smith-GambleV, UnverzagtFW, ShenJ, HendrieH (2006) Cholesterol, APOE genotype, and Alzheimer disease An epidemiologic study of Nigerian Yoruba. Neurology66, 223–227.
42.
GustafsonDR, MazzucoS, OngaroF, AntuonoP, ForloniG, AlbaniD, GajoGB, DuranteE, CaberlottoL, ZanardoA, SiculiM, GallucciM (2012) Body mass index, cognition, disability, APOE genotype, and mortality: The “Treviso Longeva” Study. Am J Geriatr Psychiatry20, 594–602.
43.
EspirituDJ, MazzoneT (2008) Oxidative stress regulates adipocyte apolipoprotein E and suppresses its expression in obesity. Diabetes57, 2992–2998.
44.
PresečkiP, Mück-ŠelerD, MimicaN, PivacN, MustapićM, StipčevićT, ŠmalcVF (2011) Serum lipid levels in patients with Alzheimer’s disease. Coll Antropol35, 115–120.
45.
VelusamyT, PanneerselvamAS, PurushottamM, AnusuyadeviM, PalPK, JainS, EssaMM, GuilleminGJ, KandasamyM (2017) Protective effect of antioxidants on neuronal dysfunction and plasticity in Huntington’s disease. Oxid Med Cell Longev2017, 3279061.
46.
LesserGT, BeeriMS, SchmeidlerJ, PurohitDP, HaroutunianV (2011) Cholesterol and LDL relate to neuritic plaques and to APOE4 presence but not to neurofibrillary tangles. Curr Alzheimer Res8, 303–312.
47.
BettermannK, ArnoldAM, WilliamsonJ, RappS, SinkK, TooleJF, CarlsonMC, YasarS, DekoskyS, BurkeGL (2012) Statins, risk of dementia, and cognitive function: Secondary analysis of the ginkgo evaluation of memory study. J Stroke Cerebrovasc Dis21, 436–444.
48.
LiG, ShoferJB, RhewIC, KukullWA, PeskindER, McCormickW, BowenJD, SchellenbergGD, CranePK, BreitnerJC, LarsonEB (2010) Age-varying association between statin use and incident Alzheimer’s disease. J Am Geriatr Soc58, 1311–1317.
49.
AnsteyKJ, LipnickiDM, LowLF (2008) Cholesterol as a risk factor for dementia and cognitive decline: A systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry16, 343–354.
50.
SolomonA, KivipeltoM, WolozinB, ZhouJ, WhitmerRA (2009) Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later. Dement Geriatr Cogn Disord28, 75–80.
