Lipoprotein Lipase HindIII Intronic Polymorphism in a Subset of Iranian Patients with Late-Onset Alzheimer's Disease

Overview

Journal Cell J

Specialty Cell Biology

Date 2013 Apr 30

PMID 23626940

Citations 5

Authors

Azadeh Sayad

Mehrdad Noruzinia

Mahdi Zamani

Mohammad Hossein Harirchian

Anoshirvan Kazemnejad

Affiliations

Soon will be listed here.

Abstract

Objective: Lipid metabolism is involved in the pathogenesis of late-onset Alzheimer's disease (LOAD). Lipoprotein lipase (LPL) is a multifunctional enzyme that plays a major role in lipid metabolism; its abnormal function seems to be related, either directly or indirectly, to the pathogenesis of many diseases such as atherosclerosis, coronary artery disease (CAD) and Alzheimer's disease (AD) . HindIII polymorphism is a common LPL genetic variant shown to increase the risk of LOAD. The present research investigates whether this polymorphism is involved in the pathogenesis of Iranian LOAD patients.

Materials And Methods: In this case control study ,allele and genotype frequencies for the HindIII polymorphism of the LPL gene in 100 patients affected with LOAD and 100 healthy controls were determined by reaction-restriction fragment length polymorphism (PCR-RFLP) and compared using the chi-square and Fisher's exact tests.

Results: LPL H+H+ genotype frequency in LOAD patients was 58%, which was significantly higher than controls (44%). There was a 1.75-fold increased risk for the development of LOAD in carriers of the H+H+ genotype compared to non-carriers (OR=1.75; 95%CI: 1.00-3.07; p=0.048). When adjusted for sex, the H+H+ genotype was more frequent in patients than controls; this difference was more remarkable in males (OR: 1.90; 95% CI: 1.08-3.34; p=0.024). The mean age of disease onset did not differ in patients with the LPL H+H+ genotype compared to unaffected individuals.

Conclusion: This study confirms the association between the H+H+ genotype with LOAD and supports the correlation of this genotype of the LPL gene with risk of developing LOAD in Iranian patients with AD.

Citing Articles

Genetic Variants of Lipoprotein Lipase and Regulatory Factors Associated with Alzheimer's Disease Risk.

Bruce K, Tang M, Reigan P, Eckel R Int J Mol Sci. 2020; 21(21).

PMID: 33172164 PMC: 7664401. DOI: 10.3390/ijms21218338.

Dyslipidemia: Genetics, lipoprotein lipase and HindIII polymorphism.

Palacio Rojas M, Prieto C, Bermudez V, Garicano C, Nunez Nava T, Martinez M F1000Res. 2018; 6:2073.

PMID: 30345000 PMC: 6171722. DOI: 10.12688/f1000research.12938.2.

Lipoprotein Lipase (LPL) Polymorphism and the Risk of Coronary Artery Disease: A Meta-Analysis.

Xie L, Li Y Int J Environ Res Public Health. 2017; 14(1).

PMID: 28275220 PMC: 5295335. DOI: 10.3390/ijerph14010084.

The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City.

Ahmadi Z, Senemar S, Toosi S, Radmanesh S J Cardiovasc Thorac Res. 2015; 7(2):63-7.

PMID: 26191394 PMC: 4492180. DOI: 10.15171/jcvtr.2015.14.

Mediterranean Fever gene analysis in the azeri turk population with familial mediterranean Fever: evidence for new mutations associated with disease.

Mohammadnejad L, Farajnia S Cell J. 2013; 15(2):152-9.

PMID: 23862117 PMC: 3712776.

References

Braun C, Daigneault R, Gaudelet S, Guimond A . Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptoms of mania: which one(s) result(s) more often from right than left hemisphere lesions?. Compr Psychiatry. 2008; 49(5):441-59. DOI: 10.1016/j.comppsych.2008.02.001. View

Myllykangas L, Polvikoski T, Sulkava R, Verkkoniemi A, Tienari P, Niinisto L . Cardiovascular risk factors and Alzheimer's disease: a genetic association study in a population aged 85 or over. Neurosci Lett. 2000; 292(3):195-8. DOI: 10.1016/s0304-3940(00)01467-1. View

Kume K, Hanyu H, Sato T, Hirao K, Shimizu S, Kanetaka H . Vascular risk factors are associated with faster decline of Alzheimer disease: a longitudinal SPECT study. J Neurol. 2011; 258(7):1295-303. DOI: 10.1007/s00415-011-5927-y. View

Sambrook J, Russell D . Rapid isolation of Mammalian DNA. CSH Protoc. 2012; 2006(1). DOI: 10.1101/pdb.prot3514. View

Salah D, Bohnet K, Gueguen R, Siest G, Visvikis S . Combined effects of lipoprotein lipase and apolipoprotein E polymorphisms on lipid and lipoprotein levels in the Stanislas cohort. J Lipid Res. 1997; 38(5):904-12. View

Baum L, Chen L, Masliah E, Chan Y, Ng H, Pang C . Lipoprotein lipase mutations and Alzheimer's disease. Am J Med Genet. 1999; 88(2):136-9. DOI: 10.1002/(sici)1096-8628(19990416)88:2<136::aid-ajmg8>3.0.co;2-d. View

Bales K, Dodart J, DeMattos R, Holtzman D, Paul S . Apolipoprotein E, amyloid, and Alzheimer disease. Mol Interv. 2004; 2(6):363-75, 339. DOI: 10.1124/mi.2.6.363. View

Doolittle M, Singh N, Chang C, Schotz M . Synthesis and regulation of lipoprotein lipase in the hippocampus. J Lipid Res. 1990; 31(7):1307-13. View

Ahn Y, Kamboh M, Hamman R, Cole S, Ferrell R . Two DNA polymorphisms in the lipoprotein lipase gene and their associations with factors related to cardiovascular disease. J Lipid Res. 1993; 34(3):421-8. View

10.

Nunez M, Peinado-Onsurbe J, Vilaro S, Llobera M . Lipoprotein lipase activity in developing rat brain areas. Biol Neonate. 1995; 68(2):119-27. DOI: 10.1159/000244227. View

11.

Blain J, Aumont N, Theroux L, Dea D, Poirier J . A polymorphism in lipoprotein lipase affects the severity of Alzheimer's disease pathophysiology. Eur J Neurosci. 2006; 24(5):1245-51. DOI: 10.1111/j.1460-9568.2006.05007.x. View

12.

Reitz C, Tang M, Schupf N, Manly J, Mayeux R, Luchsinger J . A summary risk score for the prediction of Alzheimer disease in elderly persons. Arch Neurol. 2010; 67(7):835-41. PMC: 3068839. DOI: 10.1001/archneurol.2010.136. View

13.

Fisher R, Humphries S, Talmud P . Common variation in the lipoprotein lipase gene: effects on plasma lipids and risk of atherosclerosis. Atherosclerosis. 1998; 135(2):145-59. DOI: 10.1016/s0021-9150(97)00199-8. View

14.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

15.

Fidani L, Compton D, Hardy J, Petersen R, Tangalos E, Mirtsou V . No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease. Neurosci Lett. 2002; 322(3):192-4. DOI: 10.1016/s0304-3940(02)00098-8. View

16.

Ordovas J, Wilson P, Schaefer M, Schaefer E . Apolipoprotein E isoform phenotyping methodology and population frequency with identification of apoE1 and apoE5 isoforms. J Lipid Res. 1987; 28(4):371-80. View

17.

Scacchi R, Gambina G, Broggio E, Moretto G, Ruggeri M, Corbo R . The H+ allele of the lipoprotein lipase (LPL) HindIII intronic polymorphism and the risk for sporadic late-onset Alzheimer's disease. Neurosci Lett. 2004; 367(2):177-80. DOI: 10.1016/j.neulet.2004.05.111. View

18.

Kounnas M, Moir R, Rebeck G, Bush A, Argraves W, Tanzi R . LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Cell. 1995; 82(2):331-40. DOI: 10.1016/0092-8674(95)90320-8. View

19.

Luchsinger J, Mayeux R . Cardiovascular risk factors and Alzheimer's disease. Curr Atheroscler Rep. 2004; 6(4):261-6. DOI: 10.1007/s11883-004-0056-z. View

20.

THORN J, Chamberlain J, Alcolado J, Oka K, Chan L, Stocks J . Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. Atherosclerosis. 1990; 85(1):55-60. DOI: 10.1016/0021-9150(90)90182-i. View