Apolipoprotein E gene polymorphism and its effect on anthropometric measures in normoglycemic subjects and type 2 diabetes

Journal of Diabetes & Metabolic Disorders

Mahsa M Amoli²  Javad Tavakkoly-Bazzaz¹  Bagher Larijani²  Parvin Amiri²  Mostafa Qorbani³  Hossein Fakhrzadeh²  Ozra Tabatabaei-Malazy² 

[1] Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran;Department of Epidemiology & Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

关键词: Lipid;    Diabetes mellitus;    Obesity;    Gender;    Apolipoprotein E;   

Others  :  807219
DOI  :  10.1186/2251-6581-11-18

 received in 2012-06-30, accepted in 2012-10-04,  发布年份 2012

【 摘 要 】

Background

Apolipoprotein E (apo E) plays a major role in lipid metabolism, obesity and accordingly in development of diabetes and coronary heart disease (CHD). Our main objective was to evaluate the association between apo E gene polymorphism with anthropometric measures.

Methods

Participants were selected from zone 17 Tehran/Iran. We assessed height, weight, body mass index (BMI), waist circumference (WC), blood pressure, serum fasting blood sugar, total cholesterol and triglycerides. Genotyping for apo E gene polymorphism was carried out using PCR-RFLP technique.

Results

Among total study population (n=311), 156 subjects were diabetic. The apo E3/E3 was the most common genotype in our population while E2 and E4 alleles had lower frequencies, respectively. After adjustment for diabetes, the apo E2 and E4 alleles were significantly associated with hypercholesterolemia and WC, respectively (p= 0.009, 0.034). This association was also related to sex and age. The probability of having abdominal obesity in E4 allele carriers was increased from 0.22 to 8.12 in women and to 3.08 in age ≥ 50 years.

Conclusions

Apo E polymorphism had significant influences on WC and total cholesterol level in patients with type 2 diabetes. This study highlights the importance of lifestyle modifications which may be more beneficial in hypercholesterolemic women carriers of E2 and E4 alleles concomitant central obesity.

【 授权许可】

   
2012 Tabatabaei-Malazy et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Davignon J, Cohn JS, Mabile L, Bernier L: Apolipoprotein E and atherosclerosis: insight from animal and human studies. Clin Chim Acta 1999, 286:115-143.
• [2]Schaefer EJ, Lamon-Fava S, Cohn SD, Schaefer MM, Ordovas JM, Castelli WP, et al.: Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study. J Lipid Res 1994, 35:779-792.
• [3]Song Y, Stampfer MJ, Liu S: Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med 2004, 141:137-147.
• [4]Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, et al.: Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007, 298:1300-1311.
• [5]Ingelsson E, Schaefer EJ, Contois JH, McNamara JR, Sullivan L, Keyes MJ, et al.: Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 2007, 298:776-785.
• [6]Shcherbak NS: Apolipoprotein E gene polymorphism is not a strong risk factor for diabetic nephropathy and retinopathy in type 1 diabetes: case–control study. BMC Med Genet 2001, 2:8.
• [7]Ukkola O, Kervinen K, Salmela PI, Dickhoff KV, Laakso M, Kesaniemi YA: Apolipoprotein E phenotype is related to macro- and microangiopathy in patients with non-insulin-dependent diabetes mellitus. Atheroscelerosis 1993, 101:9-15.
• [8]Mahley RW: Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988, 240:622-630.
• [9]Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Strochla BC: Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol 2002, 155:487-495.
• [10]Kalina Á, Szalai C, Prohászka Z, Reiber I, CsászVr A: Association of plasma lipid levels with apolipoprotein E polymorphism in type 2 diabetes. Diabetes Res Clin Pract 2002, 56:63-68.
• [11]Spiegelman BM, Flier JS: Obesity and the regulation of energy balance. Cell 2001, 104:531-543.
• [12]Kopelman PG: Obesity as a medical problem. Nature 2000, 404:635-643.
• [13]Grundy SM: Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab 2007, 92:399-404.
• [14]Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C: Genetic aspects of susceptibility to obesity and related dyslipidemias. Mol Cell Biochem 1992, 113:151-169.
• [15]Camelli D, Cardon LR, Fabsitz R: Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments. Am J Hum Genet 1994, 55:566-573.
• [16]Lyssenko V, Almgren P, Anevski D, Perfekt R, Lahti K, Isomaa B, et al.: Predictors and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes 2005, 54:166-174.
• [17]Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, et al.: Follow – up report on the diagnosis of diabetes mellitus. Diabetes Care 2003, 26:3160-3167.
• [18]WHO prevention and management of the global epidemic of obesity. Report of the WHO consultation on obesity[http://apps.who.int/bookorders/anglais webcite]
• [19]Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001, 285:2486-2497.
• [20]Zivelin A, Rosenberg N, Peretz H, Amit Y, Kornbrot N, Seligsohn U: Improved method for genotyping apolipoprotein E polymorphisms by a PCR-based assay simultaneously utilizing two distinct restriction enzymes. Clin Chem 1997, 43:1657-1659.
• [21]Rannala B: Finding genes influencing susceptibility to complex diseases in the postgenome era. Am J Pharmacogenomics 2001, 1:203-221.
• [22]Bayoumi R, Al-Yahyaee S, Albarwani S, Rizvi SG, Al-Hadabi S, Al-Ubaidi F, et al.: Heritability of determinants of the metabolic syndrome among healthy Arabs of “Oman Family Study”. Obesity 2007, 15:551-556.
• [23]Tabatabaei-Malazy O, Hasani-Ranjbar S, Amoli MM, Heshmat R, Sajadi M, Derakhshan R, et al.: Gender- specific differences in the association of adiponectin gene polymorphisms with body mass index. Rev Diabet Stud 2010, 7:241-246.
• [24]Bazzaz JT, Nazari M, Nazem H, Amiri P, Fakhrzadeh H, Heshmat R, et al.: Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population. J Postgrad Med 2010, 56:173-175.
• [25]Stephens JW, Sozen MM, Whittall RA, Caslake MJ, Bedford D, Acharya J, et al.: Three novel mutations in the apolipoprotein E gene in a sample of individuals with Type 2 diabetes mellitus. Clin Chem 2005, 51:119-124.
• [26]Oh J-Y, 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.
• [27]Kolovou GD, Anagnostopoulou KK, Salpea KD, Panagiotakos DP, Hoursalas IS, Cariolou MA, et al.: Apolipoprotein E genotype in matched men and women with coronary heart disease. Ann Clin Lab Sci 2005, 35:391-396.
• [28]Boer JM, Ehnholm C, Menzel HJ, Havekes LM, Rosseneu M, O’Reilly DS, et al.: Interactions between lifestyle-related factors and the apo E polymorphism on plasma lipids and apolipoproteins. The EARS Study. European Atherosclerosis Research Study. Arterioscler Thromb Vasc Biol 1997, 17:1675-1681.
• [29]Pedro-Botet J, Schaefer EJ, Bakker-Arkema RG, Black DM, Stein EM, Corella D, et al.: Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner. Atherosclerosis 2001, 158:183-193.
• [30]Kolovou GD, Anagnostopoulou KK, Kostakou P, Giannakopoulou V, Mihas C, Hatzigeorgiou G, et al.: Apolipoprotein E gene polymorphism and obesity status in middle-aged men with coronary heart disease. In Vivo 2009, 23:33-39.
• [31]Wu K, Bowman R, Welch AA, Luben RN, Wareham N, Khaw KT, et al.: Apolipoprotein E polymorphisms, dietary fat and fiber, and serum lipids: The EPIC Norfolk study. Eur Heart J 2007, 28:2930-2936.
• [32]Björntorp P: The associations between obesity, adipose tissue distribution and disease. Acta Med Scand 1988, 723:121-134.
• [33]Despres J-P, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C: Genetic aspects of susceptibility to obesity and related dyslipidemias. Mol Cell Biochem 1992, 113:1511-1569.
• [34]Laakso M, Sarlund H, Mykkänen L: Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degree of glucose tolerance. Arteriosclerosis 1990, 10:223-231.
• [35]Wilson PW, Myers RH, Larson MG, Ordovas JM, Wolf PA, Schaefer EJ: Apolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study. J Am Med Assoc 1994, 272:1666-1671.
• [36]Meigs JB, Ordovas JM, Cupples LA, Singer DE, Nathan DM, Schaefer EJ, et al.: Apolipoprotein E isoform polymorphisms are not associated with insulin resistance. The Framingham Offspring Study. Diabetes Care 2000, 23:669-674.
• [37]Dallongeville J, Lussier-Cacan S, Davignon J: Modulation of plasma triglyceride levels by apo E phenotype: a meta-analysis. J Lipid Res 1992, 33:447-454.
• [38]Raffai RL, Loeb SM, Weisgraber KH: Apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels. Arterioscler Thromb Vasc Biol 2005, 25:436-441.
• [39]Heeren J, Grewal T, Laatsch A, Becker N, Rinninger F, Rye KA, et al.: Impaired recycling of apolipoprotein E4 is associated with intracellular cholesterol accumulation. J Biol Chem 2004, 279:55483-55492.
• [40]Gajra B, Candlish JK, Saha N, Heng CK, Soemantri AG, Tay JSH: Influence of polymorphisms for apolipoprotein B (ins/del, XbaI, EcoRI) and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population. Genet Epidemiol 1994, 11:19-27.
• [41]Gajra B, Candlish JK, Saha N, Mak JW, Tay JSH: Effect of apolipoprotein E variants on plasma lipids and apolipoproteins in the Orang Asli (’Aborigines’) of Malaysia. Hum Hered 1994, 44:209-213.
• [42]Reilly SL, Ferrell RE, Sing CF: The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minn, III: correlations and covariances. Am J Hum Genet 1994, 55:1001-1008.
• [43]Xu CF, Talmud PJ, Angelico F, Ben MD, Savill J, Humphries SE: Apolipoprotein E polymorphism and plasma lipid, lipoprotein levels in Italian children. Genet Epidemiol 1991, 8:389-398.
• [44]Boemi M, Sirolla C, Testa R, Gregorio F, Brandoni G, Fumelli P, et al.: Apolipoprotein E polymorphisms and mortality in Italian type 2 diabetic patients. Eur J Clin Invest 2003, 33:296-300.
• [45]Werle E, Fiehn W, Hasslacher C: Apolipoprotein E polymorphism, and renal function in German type 1 and type 2 diabetic patients. Diabetes Care 1998, 21:994-998.
• [46]Inamdar PA, Kelkar SM, Devasagayarn TP, Bapat MM: Apolipoprotein E polymorphism in non-dependent diabetes of Mumbai, India and its effect on plasma lipids and lipoproteins. Diabetes Res Clin Pract 2000, 47:217-223.
• [47]Horita K, Eto M, Makino I: Apolipoprotein E2, renal failure and lipid abnormalities in non-insulin-dependent diabetes mellitus. Atherosclerosis 1994, 107:203-211.
• [48]Eto M, Saito M, Okada M, Kume Y, Kawasaki F, Matsuda M, et al.: Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients. Am J Kidney Dis 2002, 40:243-251.
• [49]Cobbaert C, Mulder P: Regional serum cholesterol differences in Belgium: de genetically determined cardiovascular risk factors contribute? Int J Epidemiol 1998, 27:605-613.
• [50]Volcik KA, Barkley RA, Hutchinson RG, Mosley TH, Heiss G, Sharrett AR, et al.: Apolipoprotein E polymorphisms predict low density lipoprotein cholesterol levels and carotid artery wall thickness but not incident coronary heart disease in 12,491 ARIC study participants. Am J Epidemiol 2006, 164:342-348.
• [51]Garry PJ, Baumgartner RN, Brodie SG, Montoya GD, Liang HC, Lindeman RD, et al.: Estrogen replacement therapy, serum lipids, and polymorphism of the apolipoprotein E gene. Clin Chem 1999, 45:1214-1223.
• [52]Reznik Y, Morello R, Pousse P, Mahoudeau J, Fradin S: The effect of age, body mass index, and fasting triglyceride level on postprandial lipemia is dependent on apolipoprotein E polymorphism in subjects with non-insulin-dependent diabetes mellitus. Metabolism 2002, 51:1088-1092.
• [53]Goode GK, Miller JP, Heagerty AM: Hyperlipidaemia, hypertension, and coronary heart disease. Lancet 1995, 345:362-364.
• [54]Uusitupa M, Sarkkinen E, Kervinen K, Kesaniemi YA: Apolipoprotein E phenotype and blood pressure. Lancet 1994, 343:57.