Wiener Klinische Wochenschrift

, Volume 115, Issue 1–2, pp 36–40 | Cite as

Interaction between angiotensin-converting enzyme genotype and glycaemic control influences lipoprotein levels in Type 2 diabetes mellitus

  • Ivan TkáčEmail author
  • Ján Šalagovič
  • Miriam Kozárová
  • Hana Rosolová
  • Angela Molčányiová
  • Dana Mosorjáková
  • Martina Chleborádová
  • Ivan Kalina
Original Article



To evaluate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on lipid levels in patients with Type 2 diabetes.

Patients and methods

109 patients with Type 2 diabetes were included. The patients were not on any lipid-lowering treatment. The groups with different ACE genotypes had similar ages, sex distributions, body mass indices, systolic blood pressures and indices of glycaemic control. ACE gene I/D polymorphism was determined using polymerase chain reaction.


The mean apolipoprotein B (apoB) level was significantly higher in the group of DD homozygotes compared with the subjects with at least one insertion allele (DD: 1.21±0.25 g/l vs. ID+II: 1.04±0.27 g/l;P=0.007). Significant correlations between glycated haemoglobin (HbA10) and both apoB and cholesterol levels were found (r=0.27;P<0.01). For the apoB, this correlation was highly significant in the DD-genotype subgroup (r=0.54;P<0.01), and was not significant in the subgroup of patients with genotypes ID or II. In the multivariate analysis, HbA10 and the interaction of genotype DD with HbA10 were significant independent predictors of apoB (r2=0.17) and cholesterol levels.


The present study showed that the interaction between the DD genotype of angiotensin-converting enzyme and chronic hyperglycaemia (expressed by HbA10 level) is related to higher plasma levels of atherogenic lipoproteins, such as apoB and cholesterol, in patients with Type 2 diabetes.


Angiotensin-converting enzyme polymorphism lipoproteins apolipoprotein B Type 2 diabetes mellitus glycated haemoglobin 


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  1. 1.
    Kannel WB, McGee, DL (1979) Diabetes and cardiovascular disease. The Framingham study. J Am Med Assoc 241: 2035–2038CrossRefGoogle Scholar
  2. 2.
    Reaven GM (1994) Syndrome X: 6 years later. J Intern Med 736 [Suppl]: 13–22Google Scholar
  3. 3.
    Marre M, Bernadet P, Gallois Y, Savagner F, Guyene TT, Hallab M, et al (1994) Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 43: 384–388PubMedCrossRefGoogle Scholar
  4. 4.
    Cambien F, Poirier O, Lecerf L, Evans A, Cambou J-P, Arveiler D, et al (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359: 461–464CrossRefGoogle Scholar
  5. 5.
    Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D, et al (1994) Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 91: 3662–3665PubMedCrossRefGoogle Scholar
  6. 6.
    Jeffers BW, Estacio RO, Raynolds MV, Schrier RW (1997) Angiotensin-converting enzyme polymorphism in non-in-sulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Kidney Int 52: 473–477PubMedCrossRefGoogle Scholar
  7. 7.
    Barnas U, Schmidt A, Illievich A, Kiener HP, Rabensteiner D, Kaider A, et al (1997) Evaluation of risk for the development of nephropathy in patients with IDDM: insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control. Diabetologia 40: 327–331PubMedCrossRefGoogle Scholar
  8. 8.
    Huang XH, Rantalaiho V, Wirta O, Pasternack A, Koivula T, Hiltunen T, et al (1998) Relationship of the angiotensinconverting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM, Hum Genet 102: 372–378PubMedCrossRefGoogle Scholar
  9. 9.
    Sertic J, Hebrang D, Janus D, Salzer B, Niksic M, Cvoriscec D, et al (1996) Association between deletion polymorphism of the angiotensin-converting enzyme and cerebral atherosclerosis Eur J Clin Chem Clin Biochem 34: 301–304PubMedGoogle Scholar
  10. 10.
    Oren I, Brook JG, Gershoni-Baruch R, Kepten I, Tamir A, Linn S, et al (1999) The D allele of the angiotensin-coverting enzyme gene contributes toward blood LDL-cholesterol levels and the presence of hypertension. Atherosclerosis 145: 267–271PubMedCrossRefGoogle Scholar
  11. 11.
    Katsuya T, Horiuchi M, Chen YDI, Koike G, Pratt RE, Dzau VJ, et al (1995) Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia. Arterioscler Thromb Vasc Biol 15: 779–782PubMedGoogle Scholar
  12. 12.
    Corbo RM, Vilardo T, Mantuano E, Ruggeri M, Gemma AT, Scacchi R (1999) Apolipoproteins B and E, and angiotensin I-converting enzyme genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels, Hum Biol 71: 933–945PubMedGoogle Scholar
  13. 13.
    Kobayashi K, Amemiya S, Mochizuki M, Kobayashi K, Matsushita K, Sawanabori E, et al (1999) Association of angiotensin-converting enzyme gene polymorphism with lipid profiles in children and adolescents with insulindependent diabetes mellitus. Horm Res 51: 201–204PubMedCrossRefGoogle Scholar
  14. 14.
    Nagi DK, Foy CA, Mohamed-Ali V, Yudkin JS, Grant PJ, Knowler WC (1998) Angiotensin-I-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians. Metabolism 47: 622–626PubMedCrossRefGoogle Scholar
  15. 15.
    Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al (1998) Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS 23). Br Med J 316: 823–828Google Scholar
  16. 16.
    Howard BV, Robbins DC, Sievers ML, Lee ET, Rhoades D, Devereux RB, et al (2000) LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL. The Strong Heart Study. Arterioscler Thromb Vasc Biol 20: 830–835PubMedGoogle Scholar
  17. 17.
    Wagner AM, Perez A, Calvo F, Bonet R, Castellvi A, Ordonez J (1999) Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients. Diabetes Care 22: 812–817PubMedCrossRefGoogle Scholar
  18. 18.
    Lamarche B, Tchernof A, Mauriege P, Cantin B, Dagenais GR, Lupien PJ, et al (1998) Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA — J Am Med Assoc 279: 1955–1961CrossRefGoogle Scholar
  19. 19.
    Tkáč I, Kimball BP, Lewis G, Uffelman K, Steiner G (1997) The severity of coronary atherosclerosis in type 2 diabetes mellitus is related to the number of circulating triglyceride-rich lipoprotein particles. Arterioscler Thromb Vasc Biol 17: 3633–3638PubMedGoogle Scholar
  20. 20.
    Tkáč I, Mudríková T, Szabóová E, Ďurovcová E, Lewis GF (2001) Carotid intima-media thickness in type 2 diabetes is more strongly related to serum apoprotein A-I in females. Wien Klin Wochenschr 113: 194–198PubMedGoogle Scholar
  21. 21.
    Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme accounted for half the variance of serum enzyme levels. J Clin Invest 86: 1343–1346PubMedCrossRefGoogle Scholar
  22. 22.
    Duvillard L, Pont F, Florentin E, Gambert P, Verges B (2000) Significant improvement of apolipoprotein B-containing lipoprotein metabolism by insulin treatment in patients with non-insulin-dependent diabetes mellitus. Diabetologia 43: 27–35PubMedCrossRefGoogle Scholar
  23. 23.
    Cummings MH, Watts GF, Umpleby AM, Hennessy TR, Naoumova R, Slavin BM, et al (1995) Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM. Diabetologia 38: 959–967PubMedCrossRefGoogle Scholar
  24. 24.
    Steiner G, Tkáč I, Uffelman KD, Lewis GF (1998) Important contribution of lipoprotein particle number to plasma triglyceride concentration in type 2 diabetes. Atherosclerosis 137: 211–214PubMedCrossRefGoogle Scholar
  25. 25.
    Tomkin GH, Owens D (2001) Abnormalities in apo B-containing lipoproteins in diabetes and atherosclerosis. Diabetes Metab Res Rev 17: 27–43PubMedCrossRefGoogle Scholar
  26. 26.
    Marian AJ, Safavi F, Ferlic L, Dunn JK, Gotto AM, Ballantyne CM (2000) Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. The Lipoprotein and Coronary Atherosclerosis Study. J Am Coll Cardiol 35: 89–95PubMedCrossRefGoogle Scholar
  27. 27.
    Mattei MG, Hubert C, Alhenc-Gelas F, Roeckel N, Corvol P, Soubrier F (1989) Angiotensin-I converting enzyme gene is on chromosome 17. Cytogenet Cell Genet 51: 1041Google Scholar
  28. 28.
    Haagerup A, Kristensen T, Kruse TA (1991) Polymorphism and genetic mapping of the gene encoding human beta-2-glycoprotein I to chromosome 17. Cytogenet Cell Genet 58: 2005Google Scholar
  29. 29.
    Ruiu G, Gambino R, Veglia F, Pagano G, Cassader M (1997) Influence of APOH protein polymorphism on apoH levels in normal and diabetic subjects. Clin Genet 52: 167–172PubMedCrossRefGoogle Scholar
  30. 30.
    Mehdi H, Aston CE, Sanghera DK, Hamman RF, Kamboh MI (1999) Genetic variation in the apolipoprotein H (beta2-glycoprotein I) gene affects plasma apolipoprotein H concentrations. Hum Genet 105: 63–71PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2003

Authors and Affiliations

  • Ivan Tkáč
    • 1
    Email author
  • Ján Šalagovič
    • 2
  • Miriam Kozárová
    • 1
  • Hana Rosolová
    • 3
  • Angela Molčányiová
    • 4
  • Dana Mosorjáková
    • 1
  • Martina Chleborádová
    • 2
  • Ivan Kalina
    • 2
  1. 1.Department of Medicine IV, Faculty of Medicine, Šafárik UniversityPasteur Faculty HospitalKošiceSlovakia
  2. 2.Institute of Medical Biology, Faculty of MedicineŠafárik UniversityKošiceSlovakia
  3. 3.Department of Medicine II, Faculty of Medicine in PlzeňCharles UniversityPrahaCzech Republic
  4. 4.Department of Clinical BiochemistryL. Pasteur Faculty HospitalKošiceSlovakia

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