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Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2004 Nov 12;18(6):309–316. doi: 10.1002/jcla.20044

Five polymorphisms in gene candidates for cardiovascular disease in Afro‐Brazilian individuals

Tatsuya Sakuma 2, Rosario DC Hirata 1, Mario H Hirata 1,
PMCID: PMC6807947  PMID: 15543563

Abstract

Associations of polymorphisms in the angiotensin I‐converting enzyme (ACE), apolipoprotein B (APOB) and apolipoprotein E (APOE) genes with hypertension and variations in lipid serum levels were evaluated in 184 Afro‐Brazilians with a familial history of coronary artery disease (CAD). ACE (Ins/Del) and APOB (Ins/Del, XbaI, and EcoRI) and APOE (HhaI) polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses on agarose, and polyacrylamide gel electrophoresis. Serum lipids were measured by means of routine enzymatic assays. The results showed a high frequency of hypertension (44%) in Afro‐Brazilians that was increased in subjects >40 years old and those with a blood mass index (BMI) higher than 25 kg/m2 (P<0.001). The ACE Del allele was associated with hypertension in men >40 years old (P<0.05). APOE (HhaI) and APOB (XbaI and Ins/Del) polymorphisms were not associated with hypertension or variations in serum concentrations of lipids, while subjects with the APOB E− allele had higher low‐density lipoprotein cholesterol (LDL‐C) levels than E+ carriers (P<0.05). These results suggest that ACE Ins/Del polymorphism is associated with hypertension, and APOB EcoRI polymorphism is associated with LDL‐C variation in Afro‐Brazilians. J. Clin. Lab. Anal. 18:309–316, 2004. © 2004 Wiley‐Liss, Inc.

Keywords: angiotensin I‐converting enzyme, apolipoprotein B, apolipoprotein E, polymorphism, hypertension, coronary artery disease

REFERENCES

  • 1. Wilson PW, Evans JC. Coronary artery disease prediction. Am J Hypertens 1993;6:309S–313S. [DOI] [PubMed] [Google Scholar]
  • 2. Simon A, Megnien JL, Levenson J. Coronary risk estimation and treatment of hypercholesterolemia. Circulation 1997;96:2449–2452. [DOI] [PubMed] [Google Scholar]
  • 3. Galton DJ. Genetic determinants of atherosclerosis‐related dyslipidemias and their clinical implications. Clin Chim Acta 1997;257:181–197. [DOI] [PubMed] [Google Scholar]
  • 4. Goldstein JL, Brown MS. The cholesterol quartet. Science 2001;292:1310–1312. [DOI] [PubMed] [Google Scholar]
  • 5. Winkelmann BR, Hager J. Genetic variation in coronary heart disease and myocardial infarction methodological overview and clinical evidence. Pharmacogenomics 2000;1:73–94. [DOI] [PubMed] [Google Scholar]
  • 6. Doevendans PA, Jukema W, Spiering W, Defesche JC, Kastelein JJ. Molecular genetics and gene expression in atherosclerosis. Int J Cardiol 2001;80:105–106. [DOI] [PubMed] [Google Scholar]
  • 7. Rigat B, Hubert C, Alhele‐Gelas F, et al. An insertion/deletion polymorphism in the angiotensin I‐converting enzyme gene accounting for half the variance of serum enzyme level. J Clin Invest 1990;86:1343–1346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Tiret L, Rigat B, Visvikis S, et al. Evidence from combined segregation and linkage analysis that a variant of the angiotensin I‐converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 1992;51:197–205. [PMC free article] [PubMed] [Google Scholar]
  • 9. Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin‐converting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641–644. [DOI] [PubMed] [Google Scholar]
  • 10. Evans AE, Poirier O, Kee F, et al. Polymorphism of the angiotensin‐converting‐enzyme gene in subjects who died from coronary heart disease. Q J Med 1994;87:211–214. [PubMed] [Google Scholar]
  • 11. Cambien F, Costerousse O, Tiret L, et al. Plasma level and gene polymorphism of angiotensin‐converting enzyme in relation to myocardial infarction. Circulation 1994;90:669–676. [DOI] [PubMed] [Google Scholar]
  • 12. Frield W, Krempler F, Paulweber B, Pichler M, Sandhofer F. A deletion polymorphism in the angiotensin converting enzyme gene is not associated with coronary heart disease in an Austrian population. Atherosclerosis 1995;112:137–143. [DOI] [PubMed] [Google Scholar]
  • 13. Agerholm‐Larsen B, Nordestgaard BG, Steffensen R, et al. ACE polymorphism: ischemic heart disease and longevity in 10,150 individuals. A case‐referent and retrospective cohort study based on the Copenhagen City Heart Study. Circulation 1997;95:2358–2367. [DOI] [PubMed] [Google Scholar]
  • 14. Agerholm‐Larsen B, Nordestgaard BG, Tybjaerg‐Hansen A. ACE gene polymorphism in cardiovascular disease. Meta‐analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000;20:484–492. [DOI] [PubMed] [Google Scholar]
  • 15. Chiang FT, Lai ZP, Chern TH, et al. Lack of association between angiotensin‐converting enzyme gene polymorphism and coronary heart disease in a Chinese population. Jpn Heart J 1997;38:227–236. [DOI] [PubMed] [Google Scholar]
  • 16. Fujimura T, Yokota M, Kato S, et al. Lack of association of angiotensin converting enzyme gene polymorphism or serum enzyme activity with coronary artery disease in Japanese subjects. Am J Hypertens 1997;10:1384–1390. [DOI] [PubMed] [Google Scholar]
  • 17. Barley J, Blackwood A, Miller M, et al. Angiotensin‐converting enzyme gene I/D polymorphism, blood pressure and the renin‐angiotensin system in Caucasian and Afro‐Caribbean peoples. J Hum Hypertens 1996;10:31–35. [PubMed] [Google Scholar]
  • 18. Mathew J, Basheeruddin K, Prabhakar S. Differences in frequency of the deletion polymorphism of the angiotensin‐converting enzyme gene in different ethnic groups. Angiology 2001;52:375–379. [DOI] [PubMed] [Google Scholar]
  • 19. Mahley RW, Rall SC. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000;1:507–537. [DOI] [PubMed] [Google Scholar]
  • 20. Eichner JE, Dunn ST, Preveen G, Thompson DM, Stewart KE, Stroehla CB. Apolipoprotein E polymorphism and cardiovascular disease: a huge review. Am J Epidemiol 2002;155:487–495. [DOI] [PubMed] [Google Scholar]
  • 21. Siest G, Pillot T, Régis‐Bailly A, et al. Apolipoprotein E: an important gene and protein to follow in laboratory medicine. Clin Chem 1995;41:1068–1086. [PubMed] [Google Scholar]
  • 22. Wilson PWF, Schaefer EJ, Larson MG, Ordovas JM. Apolipoprotein E alleles and risk of coronary disease. A meta‐analysis. Arterioscler Thromb Vasc Biol 1996;16:1250–1255. [DOI] [PubMed] [Google Scholar]
  • 23. Salazar LA, Hirata MH, Giannini SD, et al. Seven DNA polymorphisms at the candidate genes of atherosclerosis in Brazilian women with angiographically documented coronary artery disease. Clin Chim Acta 2000;300:139–149. [DOI] [PubMed] [Google Scholar]
  • 24. Lahoz C, Schaefer EJ, Cupples LA, et al. Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis 2001;154:529–537. [DOI] [PubMed] [Google Scholar]
  • 25. Young SG. Recent progress in understanding apolipoprotein B. Circulation 1990;82:1574–1594. [DOI] [PubMed] [Google Scholar]
  • 26. Wu JH, Wen MS, Lo SK, Chern MS. Increased frequency of apolipoprotein B signal peptide sp24/24 in patients with coronary artery disease. General allele survey in population of Taiwan and comparison with Caucasians. Clin Genet 1994;45:250–254. [DOI] [PubMed] [Google Scholar]
  • 27. Turner PR, Talmud PJ, Visvikis S, Ehnholm C, Tiret L. DNA polymorphisms of the apoprotein B gene are associated with altered plasma lipoprotein concentrations but not with perceived risk of cardiovascular disease: European Atherosclerosis Research Study. Atherosclerosis 1995;116:221–234. [DOI] [PubMed] [Google Scholar]
  • 28. Gardemann A, Ohly D, Fink M, et al. Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction. Atherosclerosis 1998;14:167–175. [DOI] [PubMed] [Google Scholar]
  • 29. Guzman EC, Hirata MH, Quintao EC, Hirata RD. Association of the apolipoprotein B gene polymorphism with cholesterol levels and response to fluvastatin in Brazilian individuals with high risk of coronary heart disease. Clin Chem Lab Med 2000;38:731–736. [DOI] [PubMed] [Google Scholar]
  • 30. Cavalli SA, Hirata MH, Salazar ET, et al. Apolipoprotein B gene polymorphisms: prevalence and impact on serum lipid concentrations in hypercholesterolemic individuals from Brazil. Clin Chim Acta 2000;302:189–203. [DOI] [PubMed] [Google Scholar]
  • 31. Machado MO, Hirata MH, Bertolami M, Hirata RDC. Apo B gene haplotype is associated with lipid profile of higher risk for coronary heart disease in Caucasian Brazilian men. J Clin Lab Anal 2001;15:19–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Gaffney D, Freeman DJ, Shepherd J, Packard CJ. The ins/del polymorphism in the signal sequence of apolipoprotein B has no effect on lipid parameters. Clin Chim Acta 1993;218:131–138. [DOI] [PubMed] [Google Scholar]
  • 33. Bydlowski SP, Novak EM, Issa JS, et al. DNA polymorphisms of apolipoprotein B and AI‐CII‐AIV genes in a Brazilian population: a preliminary report. Braz J Med Biol Res 1996;29:1269–1274. [PubMed] [Google Scholar]
  • 34. Glisic S, Prljic J, Radovanovic N, Alavantic D. Study of apoB signal peptide insertion deletion polymorphism in a healthy Serbian population: no association with serum lipid levels. Clin Chim Acta 1997;263:57–65. [DOI] [PubMed] [Google Scholar]
  • 35. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low‐density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502. [PubMed] [Google Scholar]
  • 36. III Consenso Brasillero de Hipertensso Arterial . III CBH Rev Bras Clin Ter 1998;24:231–242. [Google Scholar]
  • 37. Salazar LA, Hirata MH, Cavalli SA, Machado MO, Hirata RDC. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem 1998;44:1748–1750. [PubMed] [Google Scholar]
  • 38. Schunkert H. Polymorphism of the angiotensin‐converting enzyme gene and cardiovascular disease. J Mol Med 1997;75:867–875. [DOI] [PubMed] [Google Scholar]
  • 39. Terzic R, Letonja M, Terzic I, et al. Insertion/deletion polymorphism of angiotensin‐converting enzyme gene‐risk factor for coronary artery disease in the Tuzla region population (Bosnia and Herzegovina). Coll Antropol 2003;27:537–540. [PubMed] [Google Scholar]
  • 40. Agachan B, Isbir T, Yilmaz H, Akoglu E. Angiotensin converting enzyme I/D, angiotensin T174M‐M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. Exp Mol Med 2003;35:545–549. [DOI] [PubMed] [Google Scholar]
  • 41. Holmer SR, Bickboller H, Hengstenberg C, et al. Angiotension converting enzyme gene polymorphism and myocardial infarction: a large association and linkage study. Int J Biochem Cell Biol 2003;35:955–962. [DOI] [PubMed] [Google Scholar]
  • 42. Fuchs SC, Petter JG, Accordi MC, et al. Establishing the prevalence of hypertension. Influence of sampling criteria. Arq Bras Cardiol 2001;76:445–452. [DOI] [PubMed] [Google Scholar]
  • 43. Freitas OC, Resende de Carvalho F, Marques Neves J, et al. Prevalence of hypertension in the urban population of Catanduva, in the state of Sao Paulo, Brazil. Arq Bras Cardiol 2001;77:9–21. [DOI] [PubMed] [Google Scholar]
  • 44. Sichieri R, Oliveira MC, Pereira RA. High prevalence of hypertension among black and mulatto women in a Brazilian survey. Ethn Dis 2001;11:412–418. [PubMed] [Google Scholar]
  • 45. Ayyobi AF, Brunzell JD. Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. Am J Cardiol 2003;92:27J–33J. [DOI] [PubMed] [Google Scholar]
  • 46. Grundy SM, Brewer HB, Cleeman JL, Smith SC, Lenfant C. Definition of metabolic syndrome. Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 2004;109:433–438. [DOI] [PubMed] [Google Scholar]
  • 47. Thayer JF, Merritt MM, Sollers JJ, et al. Effect of angiotensin‐converting enzyme insertion/deletion polymorphism DD genotype on high‐frequency heart rate variability in African Americans. Am J Cardiol 2003;92:1487–1490. [DOI] [PubMed] [Google Scholar]
  • 48. Pereira AC, Mota GA, Bensenor I, Lotufo PA, Krieger JE. Effect of race, genetic population structure, and genetic mode two‐locus association studies: clustering of functional renin‐angiotensin system gene variants in hypertension association studies. Braz J Med Biol Res 2001;34:1421–1428. [DOI] [PubMed] [Google Scholar]
  • 49. Tiret L, Blanc H, Ruidavets JB, et al. Gene polymorphisms of the rennin‐angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study. Projet d'Étude des Gènes de l'Hypertension Artèrielle Sévère à Modérée Essentielle. J Hypertens 1998;16:37–44. [DOI] [PubMed] [Google Scholar]
  • 50. Oren I, Brook JG, Gershoni‐Baruch R, et al. The D allele of the angiotensin‐converting enzyme gene contributes towards blood LDL‐cholesterol levels and the presence of hypertension. Atherosclerosis 1999;145:267–271. [DOI] [PubMed] [Google Scholar]
  • 51. O'Donnell JC, Lindpaintner K, Larson GM, et al. Evidence for association and genetic linkage of the angiotensin‐converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 1999;97:1766–1772. [DOI] [PubMed] [Google Scholar]
  • 52. Todoroki M, Minami J, Ishimitsu T, Ohrui M, Masuoka H. Relation between the angiotensin‐converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects. J Hum Hypertens 2003;7:713–718. [DOI] [PubMed] [Google Scholar]
  • 53. Chauffert M, Larghero J, Ngohou‐Botum K, Cisse A, Chevenne D, Trivin F. DNA polymorphisms of apolipoprotein B in the population of Senegal. Ann Hum Genet 1997;61:525–529. [DOI] [PubMed] [Google Scholar]
  • 54. Otta MI, Cavalli SA, Hirata RDC, Nguyen NY, Hirata MH. Apolipoprotein E genotype frequencies in hypercholesterolemic and diabetic individuals. Clin Chem 1996;42:849.8665674 [Google Scholar]
  • 55. Padua‐Mansur A, Annicchino‐Bizzacchi J, Favarato D, et al. Angiotension‐converting enzyme and apolipoprotein B polymorphisms in coronary artery disease. Am J Cardiol 2000;85:1089–1093. [DOI] [PubMed] [Google Scholar]
  • 56. Scartezini M, Zago MA, Chautard‐Freire‐Maia EA, et al. The X–X–/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample. Braz J Med Biol Res 2003;36:369–375. [DOI] [PubMed] [Google Scholar]
  • 57. Corbo RM, Scachi R, Mureddu L, et al. Apolipoprotein B, apolipoprotein E, and angiotensin‐converting enzyme polymorphisms in 2 Italian populations at different risk for coronary artery disease and comparison of allele frequencies among European populations. Hum Biol 1999;71:933–945. [PubMed] [Google Scholar]
  • 58. Kamboh MI, Bunker CH, Aston CE, Nestlerode CS, McAllister AE, Ukoli FA. Genetic association of five apolipoprotein polymorphism with serum lipoprotein‐lipid levels in African blacks. Genet Epidemiol 1999;16:205–222. [DOI] [PubMed] [Google Scholar]
  • 59. Baroni MG, Berni A, Romeo S, et al. Genetic study of common variants at the ApoE, ApoAI, ApoCIII, ApoB, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD. BMC Med Genet 2003;4:8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60. Boekholdt SM, Peters RJ, Fountoulaki K, Kastelein JJ, Sijbrands EJ. Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta‐analysis. Hum Genet 2003;113:417–425. [DOI] [PubMed] [Google Scholar]
  • 61. Chiodini BD, Barlera S, Franzosi MG, et al. Apo B gene polymorphisms and coronary artery disease: a meta‐analysis. Atherosclerosis 2003;167:355–366. [DOI] [PubMed] [Google Scholar]
  • 62. Frossard PM, Obineche EN, Lestringant GG. Association of an apolipoprotein B gene marker with essential hypertension. Hypertension 1999;33:1052–1056. [DOI] [PubMed] [Google Scholar]
  • 63. Puri RD, Tewari S, Sinha N, et al. Polymorphisms in the apolipoprotein B‐100 gene: association with plasma lipid concentration and coronary artery disease. Indian Heart J 2003;55:60–64. [PubMed] [Google Scholar]
  • 64. Tan YF, Yang S, Yu RB, et al. Relationship among the XhaI and EcoRI locus polymorphisms of apolipoprotein B gene, serum lipid metabolism and gallstone disease. Zhonghua Yi Xue Za Zhi 2003;83:844–847. [PubMed] [Google Scholar]
  • 65. Katsuya T, Baba S, Ishikawa K, et al. Epsilon 4 allele of apolipoprotein E gene associates with lower blood pressure in young Japanese subjects: the Suita Study. J Hypertens 2002;20:2017–2021. [DOI] [PubMed] [Google Scholar]

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