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Apolipoprotein A5 polymorphisms in Turkish population: association with serum lipid profile and risk of ischemic stroke

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Abstract

Atherosclerosis, a major cause of ischemic stroke, may be associated with variability of triglyceride (TG) levels. Apolipoprotein A5 (APOA5) genetic polymorphisms are associated with altered TG levels. The objective of this study was to investigate the coding region polymorphisms S19W (rs3135506) and G185C (rs2075291) and the promoter region polymorphism −1131T>C (rs662799) of the APOA5 gene as risk factors for ischemic stroke in Turkish population. Study group consisted of 272 ischemic stroke patients and 123 controls. Genotypes were determined by real-time polymerase chain reaction (PCR) for S19W and PCR-restriction fragment length polymorphism analysis (PCR–RFLP) for −1131T>C and G185C. 19W allele frequency was 0.090 in stroke patients and 0.062 in controls (P = 0.191). Minor allele frequencies of −1131T>C and G185C in patients were 0.106 and 0.004, respectively, and were nearly the same in controls. Total cholesterol and LDL-cholesterol levels were significantly higher for stroke patients having at least one 19W allele compared to non-carriers. A significant difference was also found for LDL-cholesterol levels of stroke patients; higher in −1131C allele carriers compared to wild type patients. There was a trend for higher frequency of ischemic stroke among −1131C allele carrier hypertensive, diabetic or obese subjects compared to non-carriers. However, APOA5 genotypes were not associated with the risk of ischemic stroke by logistic regression analysis. The present study demonstrated that carrying rare alleles of APOA5 S19W, −1131T>C and G185C alone do not constitute a risk for ischemic stroke in the studied Turkish subjects.

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Abbreviations

APO:

Apolipoprotein

HDL:

High density lipoprotein

LDL:

Low density lipoprotein

OR:

Odds ratio

SD:

Standard deviation

SNP:

Single nucleotide polymorphism

TG:

Triglycerides

VLDL:

Very low density lipoprotein

References

  1. World Health Organization (2011) Fact Sheet No. 310. www.who.int. Accessed 30 Dec 2011

  2. Nayler WG (1995) Atherosclerosis and endothelial damage: a brief overview. Cardiovasc Drugs Ther 9(1):25–30

    Article  Google Scholar 

  3. Geurian K, Pinson JB, Weart CW (1992) The triglyceride connection in atherosclerosis. Ann Pharmacother 26(9):1109–1117

    PubMed  CAS  Google Scholar 

  4. Mahley RW, Innerarity TL, Rall SC, Weisgraber KH (1984) Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res 25(12):1277–1294

    PubMed  CAS  Google Scholar 

  5. Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173

    Article  PubMed  CAS  Google Scholar 

  6. Merkel M, Heeren J (2005) Give me A5 for lipoprotein hydrolysis! J Clin Investig 115:2694–2696

    Article  PubMed  CAS  Google Scholar 

  7. van der Vliet HN, Sammels MG, Leegwater AC et al (2001) Apolipoprotein A-V: a novel apolipoprotein associated with an early phase of liver regeneration. J Biol Chem 276:44512–44520

    Article  PubMed  Google Scholar 

  8. Pennacchio LA, Olivier M, Hubacek JA, Krauss RM, Rubin EM, Cohen JC (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038

    Article  PubMed  CAS  Google Scholar 

  9. Nabika T, Nasreen S, Kobayashi S, Masuda J (2002) The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese. Atherosclerosis 165:201–204

    Article  PubMed  CAS  Google Scholar 

  10. Endo K, Yanagi H, Araki J, Hirano C, Kobayashi KY, Tomura S (2002) Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren. Hum Genet 111:570–572

    Article  PubMed  CAS  Google Scholar 

  11. Aouizerat BE, Kulkarni M, Heilbron D et al (2003) Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids. J Lipid Res 44:1167–1173

    Article  PubMed  CAS  Google Scholar 

  12. Baum L, Tomlinson B, Thomas GN (2003) APOA5-1131T > C polymorphism is associated with triglyceride levels in Chinese men. Clin Genet 63:337–339

    Article  Google Scholar 

  13. Kao JT, Wen HC, Chien KL, Hsu HC, Lin SW (2003) A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia. Hum Mol Genet 12:2533–2539

    Article  PubMed  CAS  Google Scholar 

  14. Austin MA, Talmud PJ, Farin FM et al (2004) Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans. Biochim Biophys Acta 1688:1–9

    Article  PubMed  CAS  Google Scholar 

  15. Bi N, Yan SK, Li GP, Yin ZN, Chen BS (2004) A single nucleotide polymorphism -1131T > C in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and alters triglyceride metabolism in Chinese. Mol Genet Metab 83(3):280–286

    Article  PubMed  CAS  Google Scholar 

  16. Li GP, Wang JY, Yan SK, Chen BS, Xue H, Wu G (2004) Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population. Clin Genet 65(6):470–476

    Article  PubMed  Google Scholar 

  17. Szalai C, Keszei M, Duba J et al (2004) Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease. Atherosclerosis 173:109–114

    Article  PubMed  CAS  Google Scholar 

  18. Havasi V, Szolnoki Z, Talian G et al (2006) Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility for development of ischemic stroke. J Mol Neurosci 29(2):177–183

    Article  PubMed  CAS  Google Scholar 

  19. Hsu LA, Ko YL, Chang CJ et al (2006) Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 185:143–149

    Article  PubMed  CAS  Google Scholar 

  20. Hodoglugil U, Tanyolac S, Williamson DW, Huang Y, Mahley RW (2006) Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks. J Lipid Res 47:144–153

    Article  PubMed  CAS  Google Scholar 

  21. Tang Y, Sun P, Guo D et al (2006) A genetic variant c.553G > T in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and altered triglyceride levels in a Chinese population. Atherosclerosis 185:433–437

    Article  PubMed  CAS  Google Scholar 

  22. Komurcu-Bayrak E, Onat A, Poda M et al (2008) Gender-modulated impact of apolipoprotein A5 gene (APOA5) -1131T > C and c.56C > G polymorphisms on lipids, dyslipidemia and metabolic syndrome in Turkish adults. Clin Chem Lab Med 46(6):778–784

    Article  PubMed  CAS  Google Scholar 

  23. Li X, Su D, Zhang X, Zhang C (2011) Association of apolipoprotein A5 gene promoter region -1131T > C with risk of stroke in Han Chinese. Eur J Intern Med 22(1):99–102

    Article  PubMed  CAS  Google Scholar 

  24. Can Demirdöğen B, Türkanoğlu A, Bek S et al (2008) Paraoxonase/arylesterase ratio, PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke. Clin Biochem 41(1–2):1–9

    Article  PubMed  Google Scholar 

  25. Lahiri DK, Schnabel B (1993) DNA isolation by a rapid method from human blood samples: effects of MgCl2, EDTA, storage time, and temperature on DNA yield and quality. Biochem Genet 31:321–328

    Article  PubMed  CAS  Google Scholar 

  26. Chandak GR, Ward KJ, Yajnik CS et al (2006) Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans. BMC Med Genet 7:76

    Article  PubMed  Google Scholar 

  27. Martin S, Nicaud V, Humphries SE, Talmud PJ, EARS Group (2003) Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges. Biochim Biophys Acta 1637(3):217–225

    Article  PubMed  CAS  Google Scholar 

  28. Ariza MJ, Sánchez-Chaparro MA, Barón FJ et al (2010) Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study. BMC Med Genet 11:66

    Article  PubMed  Google Scholar 

  29. Hubacek JA, Wang WW, Skodová Z et al (2008) APOA5 Ala315 > Val, identified in patients with severe hypertriglyceridemia, is a common mutation with no major effects on plasma lipid levels. Clin Chem Lab Med 46(6):773–777

    Article  PubMed  CAS  Google Scholar 

  30. Niculescu LS, Fruchart-Najib J, Fruchart JC, Sima A (2007) Apolipoprotein A-V gene polymorphisms in subjects with metabolic syndrome. Clin Chem Lab Med 45:1133–1139

    Article  PubMed  CAS  Google Scholar 

  31. De Andrade FM, Maluf SW, Schuch JB et al (2011) The influence of the S19W SNP of the APOA5 gene on triglyceride levels in southern Brazil: interactions with the APOE gene, sex and menopause status. Nutr Metab Cardiovasc Dis 21:584–590

    Article  PubMed  Google Scholar 

  32. Lai CQ, Demissie S, Cupples LA et al (2004) Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham heart study. J Lipid Res 45:2096–2105

    Article  PubMed  CAS  Google Scholar 

  33. Ribalta J, Figuera L, Ballart JF et al (2002) Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides in familial combined hyperlipidemia. Clin Chem 48:1597–1600

    PubMed  CAS  Google Scholar 

  34. Talmud PJ, Hawe E, Martin S et al (2002) Relative contribution of variation within the ApoC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 11:3039–3046

    Article  PubMed  CAS  Google Scholar 

  35. Maasz A, Kisfali P, Horvatovich K et al (2007) Apolipoprotein A5 T-1131C variant confers risk for metabolic syndrome. Pathol Oncol Res 13:243–247

    Article  PubMed  CAS  Google Scholar 

  36. Matsunaga A, Arishima H, Niimura H et al (2007) Strong linkage disequilibrium and association of –1131T > C and c.553G > T polymorphisms of the apolipoprotein A5 gene with hypertriglyceridemia in a Japanese population. Circ J 71:746–752

    Article  PubMed  CAS  Google Scholar 

  37. Huang MC, Wang TN, Wang HS, Sung YC, Ko YC, Chiang HC (2008) The -1131T > C polymorphism in the apolipoprotein A5 gene is related to hypertriglyceridemia in Taiwanese Aborigines. Kaohsiung J Med Sci 24(4):171–179

    Article  PubMed  Google Scholar 

  38. Lai CQ, Tai ES, Tan CE et al (2003) The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. J Lipid Res 44:2365–2373

    Article  PubMed  CAS  Google Scholar 

  39. Jang Y, Paik JK, Hyun YJ et al (2009) The apolipoprotein A5–1131T > C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease. Clin Chim Acta 402(1–2):83–87

    Article  PubMed  CAS  Google Scholar 

  40. Hubacek JA, Adamkova V, Ceska R, Poledne R, Horinek A, Vrablik M (2004) New variants in the apolipoprotein AV gene in individuals with extreme triglyceride levels. Physiol Res 53:225–228

    PubMed  CAS  Google Scholar 

  41. Yin R-X, Li Y–Y, Liu W-Y, Zhang L, Wu J-Z (2011) Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels. PLoS ONE 6(3):e17954

    Article  PubMed  CAS  Google Scholar 

  42. Zhai G, Wen P, Guo L, Chen L (2006) Association of APOA5 c.553G > T polymorphism with type 2 diabetes mellitus in a Chinese population. Clin Chem Lab Med 44(11):1313–1316

    Article  PubMed  CAS  Google Scholar 

  43. Levenson J, Simon AC, Cambien FA, Beretti C (1987) Cigarette smoking and hypertension. Factors independently associated with blood hyperviscosity and arterial rigidity. Arterioscler Thromb Vasc Biol 7:572–577

    Article  CAS  Google Scholar 

  44. Lee AJ, Mowbray PI, Lowe GDO, Rumley A, Fowkes FGR, Allan PL (1998) Blood viscosity and elevated carotid intima-media thickness in men and women: the Edinburgh artery study. Circulation 97:1467–1473

    Article  PubMed  CAS  Google Scholar 

  45. de Champlain J, Wu R, Girouard H et al (2004) Oxidative stress in hypertension. Clin Exp Hypertens 26(7–8):593–601

    Article  PubMed  Google Scholar 

  46. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol: modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924

    Article  PubMed  CAS  Google Scholar 

  47. Berliner JA, Navab M, Fogelman AM et al (1995) Atherosclerosis: basic mechanisms, oxidation, inflammation, and genetics. Circulation 91:2488–2496

    Article  PubMed  CAS  Google Scholar 

  48. Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 114(12):1752–1761

    PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to Dr. Maria-Jose Ariza for sending us the DNA samples of 19SW and 19WW individuals. We also would like to thank all patients and controls who gave blood samples for this study.

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Correspondence to Birsen Can Demirdöğen.

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Can Demirdöğen, B., Şahin, E., Türkanoğlu Özçelik, A. et al. Apolipoprotein A5 polymorphisms in Turkish population: association with serum lipid profile and risk of ischemic stroke. Mol Biol Rep 39, 10459–10468 (2012). https://doi.org/10.1007/s11033-012-1926-z

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  • DOI: https://doi.org/10.1007/s11033-012-1926-z

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