Korean J Lab Med.  2006 Jun;26(3):210-216. 10.3343/kjlm.2006.26.3.210.

Apolipoprotein E Polymorphism in Ischemic Stroke Patients with Different Pathogenetic Origins

• Kang SY
• Lee WI

• KMID: 2238889
• DOI: http://doi.org/10.3343/kjlm.2006.26.3.210

Abstract

BACKGROUND: The association of apolipoprotein E (apoE) polymorphism with interindividual variability of serum lipid concentrations and the initiation and progression of atherosclerosis is inconclusive. This study was performed to explore the associations of apoE with lipid concentrations and ischemic stroke in patients with large artery atherosclerosis (LAA) subgroup or without atherosclerotic vascular lesions (small artery occlusion, SAO) subgroup through a case-control study among the Korean population.
METHODS
The ischemic stroke group (n=194) was subdivided into an LAA subgroup (n=112) and a SAO without atherosclerotic lesion subgroup (n=82). An age-matched healthy control group (n=168) was recruited. Serum lipid concentrations were measured and apoE genotypes were determined by real-time PCR and melting curve analysis with the LightCycler (Roche Diagnostics).
RESULTS
The frequency of the epsilon4 carriers was significantly higher in the ischemic stroke group (22.7%) than in the control group (11.9%) (P=0.01). However, the frequency of 4 carriers showed no difference between the LAA and SAO subgroups (22.3% vs 23.2%, P=0.89). The adjusted low density lipoprotein cholesterol (LDLc) concentration was significantly higher in ischemic stroke group than in control group (P=0.04), but showed no significant differences in all lipid concentrations between the LAA and SAO subgroups. LDLc concentrations were lower in epsilon2 carriers than in epsilon3 and epsilon4 alleles, but showed no difference between the epsilon4 carriers and epsilon3 allele.
CONCLUSIONS
Although there was an association between the epsilon4 allele and ischemic stroke and between the LDLc concentration and ischemic stroke, there was no significant difference in the lipid concentrations and distribution of apoE genotypes between the LAA and SAO subgroups. Therefore, the epsilon4 allele may have different effects on the ischemic stroke that are independent of the atherosclerotic mechanism by high LDLc concentration.

Keyword

Apolipoprotein E polymorphism; Ischemic stroke; Lipid concentrations

MeSH Terms

Alleles
Apolipoproteins E
Apolipoproteins*
Arteries
Atherosclerosis
Case-Control Studies
Cholesterol, LDL
Freezing
Genotype
Humans
Real-Time Polymerase Chain Reaction
Stroke*
Apolipoproteins
Apolipoproteins E
Cholesterol, LDL

Reference

References

1. Catto AJ, McCormack LJ, Mansfield MW, Carter AM, Bamford JM, Robinson P, et al. Apolipoprotein E polymorphism in cerebrovascular disease. Acta Neurol Scand. 2000; 101:399–404.

2. Paik YK, Chang DJ, Reardon CA, Davies GE, Mahley RW, Taylor JM. Nucleotide sequence and structure of the human apolipoprotein E gene. Proc Natl Acad Sci USA. 1985; 82:3445–9.

3. Couderc R, Mahieux F, Bailleul S, Fenelon G, Mary R, Fermanian J. Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease: a case-control study. Stroke. 1993; 24:661–4.

4. Kim JS, Han SR, Chung SW, Kim BS, Lee KS, Kim YI, et al. The apolipoprotein E epsilon4 haplotype is an important predictor for recurrence in ischemic cerebrovascular disease. J Neurol Sci. 2003; 206:31–7.

5. Taira K, Bujo H, Hirayama S, Yamazaki H, Kanaki T, Takahashi K, et al. LR11, a mosaic LDL receptor family member, mediates the uptake of ApoE-rich lipoproteins in vitro. Arterioscler Thromb Vasc Biol. 2001; 21:1501–6.

6. Kamboh MI, Aston CE, Ferrell RE, Hamman RF. Impact of apolipoprotein E polymorphism in determining interindividual variation in total cholesterol and low density lipoprotein cholesterol in Hispanics and non-Hispanic whites. Atherosclerosis. 1993; 98:201–11.

7. Xhignesse M, Lussier-Cacan S, Sing CF, Kessling AM, Davignon J. Influences of common variants of apolipoprotein E on measures of lipid metabolism in a sample selected for health. Arterioscler Thromb. 1991; 11:1100–10.

8. Treger I, Froom P, Ring H, Friedman G. Association between apolipoprotein E4 and rehabilitation outcome in hospitalized ischemic stroke patients. Arch Phys Med Rehabil. 2003; 84:973–6.

9. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988; 8:1–21.

10. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985; 37:268–85.

11. Ehnholm C, Lukka M, Kuusi T, Nikkila E, Utermann G. Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations. J Lipid Res. 1986; 27:227–35.

12. Dallongeville J, Lussier-Cacan S, Davignon J. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis. J Lipid Res. 1992; 33:447–54.

13. Yoshida H, Hasty AH, Major AS, Ishiguro H, Su YR, Gleaves LA, et al. Isoform-specific effects of apolipoprotein E on atherogenesis: gene transduction studies in mice. Circulation. 2001; 104:2820–5.

14. Murphy MM, Vilella E, Ceruelo S, Figuera L, Sanchez M, Camps J, et al. The MTHFR C677T, APOE, and PON55 gene polymorphisms show relevant interactions with cardiovascular risk factors. Clin Chem. 2002; 48:372–5.

15. Margaglione M, Seripa D, Gravina C, Grandone E, Vecchione G, Cappucci G, et al. Prevalence of apolipoprotein E alleles in healthy subjects and survivors of ischemic stroke: an Italian case-control study. Stroke. 1998; 29:399–403.

16. MacLeod MJ, De Lange RP, Breen G, Meiklejohn D, Lemmon H, Clair DS. Lack of association between apolipoprotein E genoype and ischaemic stroke in a Scottish population. Eur J Clin Invest. 2001; 31:570–3.

17. McCarron MO, Delong D, Alberts MJ. APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis. Neurology. 1999; 53:1308–11.

18. Luthra K, Prasad K, Kumar P, Dwivedi M, Pandey RM, Das N. Apolipoprotein E gene polymorphism in cerebrovascular disease: a case-control study. Clin Genet. 2002; 62:39–44.

19. Slooter AJ, Cruts M, Hofman A, Koudstaal PJ, van der Kuip D, de Ridder MA, et al. The impact of APOE on myocardial infarction, stroke, and dementia: the Rotterdam Study. Neurology. 2004; 62:1196–8.

20. Kolovou GD, Daskalova DCh, Hatzivassiliou M, Yiannakouris N, Pilatis ND, Elisaf M, et al. The epsilon 2 and 4 alleles of apolipoprotein E and ischemic vascular events in the Greek population-implications for the interpretation of similar studies. Angiology. 2003; 54:51–8.

21. Souza DR, Campos BF, Arruda EF, Yamamoto LJ, Trindade DM, Tognola WA. Influence of the polymorphism of apolipoprotein E in cerebral vascular disease. Arq Neuropsiquiatr. 2003; 61:7–13.

22. Kim JS, Han SR, Chung SW, Kim KS, Kim JW, Kim BS. Apolipoprotein E4 genotype in patient with ischemic cerebrovascular disease in Korea – a preliminary study. J Korean Neurol Assoc. 2001; 19:19–23.

23. McCarron MO, Muir KW, Nicoll JA, Stewart J, Currie Y, Brown K, et al. Prospective study of apolipoprotein E genotype and functional outcome following ischemic stroke. Arch Neurol. 2000; 57:1480–4.

24. Adams HP Jr, Woolson RF, Biller J, Clarke W. Studies of Org 10172 in patients with acute ischemic stroke. TOAST Study Group. Haemostasis. 1992; 22:99–103.

25. Hixson JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1991; 11:1237–44.

26. Cattin L, Fisicaro M, Tonizzo M, Valenti M, Danek GM, Fonda M, et al. Polymorphism of the apolipoprotein E gene and early carotid atherosclerosis defined by ultrasonography in asymptomatic adults. Arterioscler Thromb Vasc Biol. 1997; 17:91–4.

27. Kokubo Y, Chowdhury AH, Date C, Yokoyama T, Sobue H, Tanaka H. Age-dependent association of apolipoprotein E genotypes with stroke subtypes in a Japanese rural population. Stroke. 2000; 31:1299–306.

28. Zhang JG, Dong XZ, Yang WJ, Lu Q, He L. Population distributions of allele frequency of apolipoprotein E by age and gender in Han Chinese. Zhongguo Yao Li Xue Bao. 1999; 20:218–22.

29. Eggertsen G, Tegelman R, Ericsson S, Angelin B, Berglund L. Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations. Clin Chem. 1993; 39:2125–9.

30. Shin MH, Kim HN, Cui LH, Kweon SS, Park KS, Heo H, et al. The effect of apolipoprotein E polymorphism on lipid levels in Korean adults. J Korean Med Sci. 2005; 20:361–6.