Apolipoprotein E Polymorphism is Associated with Age of Onset in Schizophrenia

Overview

Journal J Hum Genet

Specialty Genetics

Date 2004 Jun 29

PMID 15221639

Citations 8

Authors

Olli Kampman

Sami Anttila

Ari Illi

Kari M Mattila

Riikka Rontu

Esa Leinonen

Terho Lehtimaki

Affiliations

Soon will be listed here.

Abstract

The aims of the study were to investigate the relationship between Apolipoprotein E (APOE) polymorphism, risk of schizophrenia, treatment response to conventional anti-psychotics, and age of onset in schizophrenia. The sample comprised 94 Finnish patients with a DSM-IV diagnosis of schizophrenia. Forty-three of the patients were good responders to conventional anti-psychotics and 51 were classified as non-responders. The control group consisted of 98 healthy blood donors. The APOE allele frequencies (epsilon 2, epsilon 3, and epsilon 4) were 4.8, 72.3, and 22.9% in patients and 7.1, 75.0, and 17.9 in controls. None of the differences between groups were statistically significant. No association between treatment response and APOE genotype was found. Patients with APOE epsilon 4/epsilon 4 genotype had a markedly lower age of onset compared with rest of the sample (p=0.0015), which remained significant when controlling for gender (p=0.02). There was an increasing linear trend between the number of epsilon 3 alleles (0, 1, or 2) and age of onset in schizophrenia (p=0.08). An inverse trend was found between the number of epsilon 4 alleles and age of onset (p=0.07). No relationship between APOE polymorphism and risk for schizophrenia was found. APOE epsilon 4/epsilon 4 genotype may be associated with early onset schizophrenia. APOE epsilon 3 allele may function protectively in later onset in this disease.

Citing Articles

Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes.

Sfera A, Imran H, Sfera D, Anton J, Kozlakidis Z, Hazan S Int J Mol Sci. 2024; 25(11).

PMID: 38892092 PMC: 11173215. DOI: 10.3390/ijms25115904.

The genetic basis of onset age in schizophrenia: evidence and models.

Zhan N, Sham P, So H, Lui S Front Genet. 2023; 14:1163361.

PMID: 37441552 PMC: 10333597. DOI: 10.3389/fgene.2023.1163361.

Homozygosity in the 3 Polymorphism Is Associated With Less Depression and Higher Serum Low-Density Lipoprotein in Chinese Elderly Schizophrenics.

Li W, Ban C, Yue L, Sun L, Li X, Xiao S Front Endocrinol (Lausanne). 2020; 11:642.

PMID: 33178131 PMC: 7593819. DOI: 10.3389/fendo.2020.00642.

Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson's disease: A Preliminary Study.

Gupta A, Rani K, Swarnkar S, Kumar G, Khan M, Pokhriyal R J Cent Nerv Syst Dis. 2018; 10:1179573518803585.

PMID: 30327579 PMC: 6178121. DOI: 10.1177/1179573518803585.

Verbal memory improvement in first-episode psychosis -ε4 carriers: a pleiotropic effect?.

Vila-Rodriguez F, Lang D, Baitz H, Gicas K, Thorton A, Ehmann T Neuropsychiatr Dis Treat. 2017; 13:2945–2953.

PMID: 29263671 PMC: 5727104. DOI: 10.2147/NDT.S150488.

References

Harrington C, Roth M, Xuereb J, McKenna P, Wischik C . Apolipoprotein E type epsilon 4 allele frequency is increased in patients with schizophrenia. Neurosci Lett. 1995; 202(1-2):101-4. DOI: 10.1016/0304-3940(95)12218-4. View

Mahley R, Rall Jr S . Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2001; 1:507-37. DOI: 10.1146/annurev.genom.1.1.507. View

Arnold S, Joo E, Martinoli M, Roy N, Trojanowski J, Gur R . Apolipoprotein E genotype in schizophrenia: frequency, age of onset, and neuropathologic features. Neuroreport. 1997; 8(6):1523-6. DOI: 10.1097/00001756-199704140-00040. View

Weisgraber K, Rall Jr S, Mahley R . Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J Biol Chem. 1981; 256(17):9077-83. View

Thomas E, Laws S, Sutcliffe J, Harper C, Dean B, McClean C . Apolipoprotein D levels are elevated in prefrontal cortex of subjects with Alzheimer's disease: no relation to apolipoprotein E expression or genotype. Biol Psychiatry. 2003; 54(2):136-41. DOI: 10.1016/s0006-3223(02)01976-5. View

Fisman M, Rabheru K, Hegele R, Sharma V, Fisman D, Doering M . Apolipoprotein E polymorphism and response to electroconvulsive therapy. J ECT. 2001; 17(1):11-4. DOI: 10.1097/00124509-200103000-00003. View

Pickar D, Malhotra A, Rooney W, Breier A, Goldman D . Apolipoprotein E epsilon 4 and clinical phenotype in schizophrenia. Lancet. 1997; 350(9082):930-1. DOI: 10.1016/S0140-6736(05)63266-7. View

Dean B, Laws S, Hone E, Taddei K, Scarr E, Thomas E . Increased levels of apolipoprotein E in the frontal cortex of subjects with schizophrenia. Biol Psychiatry. 2003; 54(6):616-22. DOI: 10.1016/s0006-3223(03)00075-1. View

Jonsson E, Lannfelt L, Engvall B, Sedvall G . Lack of association between schizophrenia and the apolipoprotein E epsilon 4 allele. Eur Arch Psychiatry Clin Neurosci. 1996; 246(4):182-4. DOI: 10.1007/BF02188951. View

10.

Sutcliffe J, Thomas E . The neurobiology of apolipoproteins in psychiatric disorders. Mol Neurobiol. 2002; 26(2-3):369-88. DOI: 10.1385/mn:26:2-3:369. View

11.

Livak K . Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet Anal. 1999; 14(5-6):143-9. DOI: 10.1016/s1050-3862(98)00019-9. View

12.

Siest G, Pillot T, Leininger-Muller B, Steinmetz J, Galteau M, Visvikis S . Apolipoprotein E: an important gene and protein to follow in laboratory medicine. Clin Chem. 1995; 41(8 Pt 1):1068-86. View

13.

Igata T, Ishizuka K, Kimura T, Sakamoto S, Katsuragi S, Takamatsu J . Apolipoprotein E genotype and psychosis. Biol Psychiatry. 1997; 41(8):906-8. DOI: 10.1016/S0006-3223(97)00015-2. View

14.

Hong C, Yu Y, Lin C, Song H, Lai H, Yang K . Association study of apolipoprotein E epsilon4 with clinical phenotype and clozapine response in schizophrenia. Neuropsychobiology. 2000; 42(4):172-4. DOI: 10.1159/000026689. View

15.

Gerdes L . The common polymorphism of apolipoprotein E: geographical aspects and new pathophysiological relations. Clin Chem Lab Med. 2003; 41(5):628-31. DOI: 10.1515/CCLM.2003.094. View

16.

Kimura T, Yokota S, Shono M, Takamatsu J, Miyakawa T . Apolipoprotein E epsilon2 allele and early onset schizophrenia. Neurosci Lett. 1997; 231(1):53-5. DOI: 10.1016/s0304-3940(97)00535-1. View

17.

Saiz P, Morales B, G-Portilla M, Alvarez V, Coto E, Fernandez J . Apolipoprotein E genotype and schizophrenia: further negative evidence. Acta Psychiatr Scand. 2002; 105(1):71-5. DOI: 10.1034/j.1600-0447.2002.10488.x. View

18.

Dalman C, Broms J, Cullberg J, Allebeck P . Young cases of schizophrenia identified in a national inpatient register--are the diagnoses valid?. Soc Psychiatry Psychiatr Epidemiol. 2002; 37(11):527-31. DOI: 10.1007/s00127-002-0582-3. View

19.

Hata T, Kunugi H, Nanko S, Fukuda R, Kaminaga T . Possible effect of the APOE epsilon 4 allele on the hippocampal volume and asymmetry in schizophrenia. Am J Med Genet. 2002; 114(6):641-2. DOI: 10.1002/ajmg.10556. View

20.

Murphy G, Kremer C, Rodrigues H, Schatzberg A . The apolipoprotein E epsilon4 allele and antidepressant efficacy in cognitively intact elderly depressed patients. Biol Psychiatry. 2003; 54(7):665-73. DOI: 10.1016/s0006-3223(03)00174-4. View