Journal List > Korean Diabetes J > v.32(1) > 1002230

TOOLS
Lee, Jang, Kim, Kim, Lee, Choi, Lim, Park, Park, and Kim: Association between Apolipoprotein E Polymorphism and Type 2 Diabetes in Subjects Aged 65 or Over
Original Article
Korean Diabetes Journal

Korean Diabetes Journal 2008; 32(1): 30-37.

Published online: 29 February 2008

DOI: https://doi.org/10.4093/kdj.2008.32.1.30

Association between Apolipoprotein E Polymorphism and Type 2 Diabetes in Subjects Aged 65 or Over

You Jin Lee, Hak Chul Jang, Eun Hye Kim3, Hye Jin Kim3, Seok Bum Lee1, Sung Hee Choi, Soo Lim, Kyoung Un Park2, Young Joo Park, Ki Woong Kim1

Department of Internal Medicine, Seoul National University of College of Medicine, Korea.

1Department of Neuropsychiatry, Seoul National University of College of Medicine, Korea.

2Department of Laboratory Medicine, Seoul National University of College of Medicine, Korea.

3Medical Science Research Institute, Seoul National University Bundang Hospital, Seoul National University of College of Medicine, Korea.

Received 29 November 2007       Accepted 8 January 2008

Copyright © 2008 Korean Diabetes Association

Abstract

Background

Increased prevalence of diabetes in recent years is linked with increased cardiovascular morbidity and mortality. Apolipoprotein E (apo E) polymorphism is well known to be related to hyperlipidemia and coronary heart disease, but only a few studies investigated the association between apo E polymorphism and diabetes or insulin resistance. In Korea, two studies with relatively small subjects reported controversial results. Therefore, we investigated the association between apo E polymorphism and diabetes in elderly community population.

Methods

982 elderly people aged 65 or over in Seongnam city were enrolled. We measured anthropometric variables and blood pressure and performed biochemical tests including fasting glucose, fasting insulin, HbA1c, and lipid profiles. Apo E polymorphism was determined by PCR-RFLP method.

Results

Frequencies of apo E isoforms and alleles were similar to those of other reports. Subjects with e4 allele had significantly higher total and LDL-cholesterol levels. However, there were no differences in cholesterol levels between normal subjects and diabetes. Diabetes was not related to apo E polymorphism.

Conclusion

In Korean aged 65 or over, subjects with diabetes didn't have increased total or LDL-cholesterol, triglyceride, and decreased HDL-cholesterol levels. Diabetes and apo E polymorphism were not related.

Keywords: Apolipoprotein E, Diabetes, Elderly, Polymorphism

Figures and Tables

Table 1
Apo E isoform frequency and allele frequency in normal subjects and diabetic subjects
kdj-32-30-i001
Table 2
Clinical and metabolic characteristics of subjects according to apo E isoformsClinical and metabolic characteristics of subjects according to apo E isoforms
kdj-32-30-i002

Values are the mean ± SD. *P < 0.05 versus e3/e3 isoform. HDL-cholesterol, high density lipoprotein-cholesterol; LDL-cholesterol, low density lipoprotein cholesterol.

Table 3
Comparison of clinical and metabolic charateristics between subjects with normal glucose tolerance and with diabetes
kdj-32-30-i003

HDL-cholesterol, high density lipoprotein-cholesterol; LDL-cholesterol, low density lipoprotein cholesterol.

Table 4
Clinical and metabolic characteristics of subjects according to apo E isoforms in diabetes group
kdj-32-30-i004

Values are the mean ± SD. *P < 0.05 versus e3/e3 isoform. HDL-cholesterol, high density lipoprotein-cholesterol; LDL-cholesterol, low density lipoprotein cholesterol.

Table 5
Logistical regression analysis examining the association between apo E isoforms, alleles and the presence of diabetes in aged people
kdj-32-30-i005

CI, Confidence Interval. e3 allele and e3/e3 isoform were used as control, respectively. Data were adjusted for age and sex.

References

1. Schernthaner G. Cardiovascular mortality and morbidity in type-2 diabetes mellitus. Diabetes Res Clin Pract. 1996. 31:Suppl. S3–S13.
2. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998. 316:823–828.
3. Rall SC Jr, Weisgraber KH, Mahley RW. Human apolipoprotein E. The complete amino acid sequence. J Biol Chem. 1982. 257:4171–4178.
4. Stiefel P, Montilla C, Muniz-Grijalvo O, Garcia-Lozano R, Alonso A, Miranda ML, Pamies E, Villar J. Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium counter transport activity in essential hypertension. Metabolism. 2001. 50:157–160.
5. Oh JY, Barrett-Connor E. Apolipoprotein E polymorphism and lipid levels differ by gender and family history of diabetes: the Rancho Bernardo Study. Clin Genet. 2001. 60:132–137.
6. Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988. 240:622–630.
7. Olaisen B, Teisberg P, Gedde-Dahl T Jr. The locus for apolipoprotein E (apoE) is linked to the complement component C3 (C3) locus on chromosome 19 in man. Hum Genet. 1982. 62:233–236.
8. Rodrigo E, Gonzalez-Lamuno D, Ruiz JC, Fernandez-Fresnedo G, Isla D, Gonzalez-Cotorruelo J, Zubimendi JA, De Francisco AL, Garcia-Fuentes M, Arias M. Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation. Am J Transplant. 2002. 2:343–348.
9. Morbois-Trabut L, Chabrolle C, Garrigue MA, Lasfargues G, Lecomte P. Apolipoprotein E genotype and plasma lipid levels in Caucasian diabetic patients. Diabetes Metab. 2006. 32:270–275.
10. Viitanen L, Pihlajamaki J, Miettinen R, Karkkainen P, Vauhkonen I, Halonen P, Kareinen A, Lehto S, Laakso M. Apolipoprotein E gene promoter (-219G/T) polymorphism is associated with premature coronary heart disease. J Mol Med. 2001. 79:732–737.
11. Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U, Danesh J. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 2007. 298:1300–1311.
12. Ranjith N, Pegoraro RJ, Rom L, Rajput MC, Naidoo DP. Lp(a) and apoE polymorphisms in young South African Indians with myocardial infarction. Cardiovasc J S Afr. 2004. 15:111–117.
13. Heininger K. A unifying hypothesis of Alzheimer's disease. III. Risk factors. Hum Psychopharmacol. 2000. 15:1–70.
14. Leiva E, Mujica V, Orrego R, Prieto M, Arredondo M. Apolipoprotein E polymorphism in type 2 diabetic patients of Talca, Chile. Diabetes Res Clin Pract. 2005. 68:244–249.
15. Camsari A, Tamer L, Aras Ates N, Pekdemir H, Cicek D, Ercan B, Camdeviren H, Atik U. Apolipoprotein E polymorphism in diabetic and non-diabetic patients: does it really contribute to atherosclerosis? Acta Cardiol. 2005. 60:409–414.
16. Duman BS, Ozturk M, Yilmazer S, Hatemi H. Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus: allele frequency and relation to serum lipid concentrations. Diabetes Nutr Metab. 2004. 17:267–274.
17. Eto M, Watanabe K, Iwashima Y, Morikawa A, Oshima E, Sekiguchi M, Ishii K. Apolipoprotein E polymorphism and hyperlipemia in type II diabetics. Diabetes. 1986. 35:1374–1382.
19. Park JH, Lim S, Lim JY, Kim KI, Yoon IY, Kim JM, Chang YS, Chang CB, Chin HJ, Choi EA, Lee SB, Park YJ, Paik NJ, Kim TK, Jang HC, Kim KW. An overview of the Korean Longitudinal Study on Health and Aging. Psychiatry Invest. 2007. 4:84–95.
20. Americal Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007. 30:Suppl 1. S42–S47.
21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985. 28:412–419.
22. 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.
23. Meigs JB, Ordovas JM, Cupples LA, Singer DE, Nathan DM, Schaefer EJ, Wilson PW. Apolipoprotein Eisoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study. Diabetes Care. 2000. 23:669–674.
24. Kim JH, Lee EJ, Kwon OH. Apolipoprotein E genotyping and phenotyping in type II diabetes mellitus patients with hypertriglyceridemia. Clin Biochem. 1997. 30:47–52.
25. Errera FI, Silva ME, Yeh E, Maranduba CM, Folco B, Takahashi W, Pereira AC, Krieger JE, Passos-Bueno MR. Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients. Braz J Med Biol Res. 2006. 39:883–888.
26. Tavintharan S, Lim SC, Chan YH, Sum CF. Apolipoprotein E genotype affects the response to lipid-lowering therapy in Chinese patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2007. 9:81–86.
27. Boemi M, James RW, Romagnoli F, Gerber P, Pometta D, Fumelli P. Gender differences in a type 2 (non-insulin-dependent) diabetic population with respect to apolipoprotein E phenotype frequencies. Diabetologia. 1993. 36:229–233.
28. Gadi R, Samaha FF. Dyslipidemia in type 2 diabetes mellitus. Curr Diab Rep. 2007. 7:228–234.
29. Biesbroeck RC, Albers JJ, Wahl PW, Weinberg CR, Bassett ML, Bierman EL. Abnormal composition of high density lipoproteins in non-insulin-dependent diabetics. Diabetes. 1982. 31:126–131.
30. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988. 37:1595–1607.
31. Brunzell JD, Porte D Jr, Bierman EL. Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated with hyper-triglyceridemia. Metabolism. 1979. 28:901–907.
TOOLS
Similar articles