Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 118  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Article Submission Resources Sections Etcetera Contact
 
  NAVIGATE Here 
  Search
 
 :: Next article
 :: Previous article 
 :: Table of Contents
  
 RESOURCE Links
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (339 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Materials and Me...
 ::  Results
 ::  Discussion
 ::  Acknowledgment
 ::  References
 ::  Article Tables

 Article Access Statistics
    Viewed4012    
    Printed131    
    Emailed1    
    PDF Downloaded170    
    Comments [Add]    
    Cited by others 6    

Recommend this journal


 


 
ORIGINAL ARTICLE
Year : 2010  |  Volume : 56  |  Issue : 3  |  Page : 173-175

Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population


1 Department of Medical Genetics, School of Medicine; Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Science, Payamnoor University, Tehran, Iran
3 Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission04-Oct-2009
Date of Decision01-Mar-2010
Date of Acceptance28-Mar-2010
Date of Web Publication23-Aug-2010

Correspondence Address:
M M Amoli
Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, Tehran
Iran
Login to access the Email id


DOI: 10.4103/0022-3859.68629

PMID: 20739760

Get Permissions


 :: Abstract 

Background: Apolipoprotein E (APOE) is known as a major regulator of blood lipid levels in humans. A number of APOE gene allelic variants have been reported including E2, E3 and E4. Recent studies suggested a role for APOE in obesity and increased Body Mass Index (BMI) and plasma lipid levels in obese children. Aim: The aim of this study was to examine the association between APOE genetic variants and the BMI and lipid profile in an Iranian cohort. Setting and Design: Samples were obtained from subjects who participated in a study based on the WHO-designed MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study for coronary artery disease risk assessment in Zone 17 of Tehran. The study was approved by the local ethical committee. Informed consent was obtained from all subjects included in this study. Materials and Methods: Subjects (n=320) were recruited. The level of triglyceride (TG) and total serum cholesterol was tested for all subjects in this study. Genotyping for APOE was carried using polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP)technique. Statistical Analysis: Levels of significance were determined using contingency tables by either Chi-square or Fisher exact analysis using the STATA (v8) software. The analysis of regression and significance of differences for level of cholesterol and TG was established by one-way analysis of variance followed by Dunnett post hoc multiple comparison tests using SPSS software Version 11.5. Results: The frequency of allele E2 was significantly higher in patients with total serum cholesterol level <200 mg/dl (P 0.01 OR 2.1 95% CI 1.1-4.2). Conclusion: The association found in this study between allele E2 and lower total cholesterol level had been reported in previous studies. We have also observed that the frequency of genotype E2/E3 and E2/E4 was significantly higher in patients with normal total serum cholesterol level compared to patients with abnormal cholesterol (P=0.003 OR 2.4 95% CI; 1.3-4.6). Our data needs to be repeated in a larger population with more information for serum LDL and HDL levels and their subgroups.


Keywords: Apolipoprotein, cholesterol, diabetes


How to cite this article:
Bazzaz J T, Nazari M, Nazem H, Amiri P, Fakhrzadeh H, Heshmat R, Abbaszadeh S, Amoli M M. Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population. J Postgrad Med 2010;56:173-5

How to cite this URL:
Bazzaz J T, Nazari M, Nazem H, Amiri P, Fakhrzadeh H, Heshmat R, Abbaszadeh S, Amoli M M. Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population. J Postgrad Med [serial online] 2010 [cited 2014 Oct 1];56:173-5. Available from: http://www.jpgmonline.com/text.asp?2010/56/3/173/68629



 :: Introduction Top


Apolipoprotein E (APOE) is known as one of the elements of major lipoproteins including chylomicron (CM), very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and also a part of high density lipoprotein (HDL). [1] The uptake of these particles by their receptors in the liver and their removal is mediated by APOE. [2] This explains the role of APOE in human cholesterol and triglyceride (TG) homeostasis. APOE has been suggested as a major regulator of blood lipid levels in humans. [3],[4]

A number of APOE gene allelic variants including E2, E3 and E4 and six different genotypes (E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4) have been reported. The properties of the two APOE binding domains differ according to these three isoforms, leading to functional differences. [5] It has been established in many reports that the presence of allele E4 (APOE c471TNC, rs 429358) is associated with increased levels of total and LDL serum cholesterol, while allele E2 (APOE c609CNT, rs7412) seems to be related to low levels of LDL and increased concentrations of plasma TG and lipoprotein remnants. [5]

Recent studies have suggested a role for APOE in obesity. [6],[7] Zhang et al.,[8] in an association study have shown that the E4 allele of APOE was significantly associated with increased body mass index (BMI) and plasma lipid levels in obese children.

The aim of this study was to examine the association between APOE genetic variants and lipid profile in an Iranian population.


 :: Materials and Methods Top


Subjects n=320 (age between 25 and 64 years) were recruited from Zone 17 of Tehran who participated in a study based on the WHO-designed MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study for coronary artery disease risk assessment. The study was approved by the institutional ethical committee written, informed consent was obtained from all subjects. There were 105 males, and 215 females.

The mean age was 45.7±13 years and mean BMI was 29.6±5.5.

Level of TG and cholesterol were tested for all our subjects using standard enzymatic methods (Pars Azmun, Iran). Body weight and height were measured twice with standard scale and at first their means and BMI calculated as body weight /square height (kg/m2).

DNA was purified from leukocytes by the salting-out method. Genotyping for APOE was carried out as described previously. [9] In brief, genomic DNA was amplified by PCR with the primers F5'-TCCAA GGAGC TGCAG GCGGC GCA and R5'-GCCCC GGCCT GGTAC ACTGC CA to yield a 218-bp DNA fragment that spans both APOE polymorphic sites. Simultaneous digestion of the 218-bp amplified product by AflIII and HaeII enzymes yielded 145-bp, 168-bp, and 195-bp fragments that were specific for Apo E3, E2, and E4, respectively.

Statistical analysis

Strength of association between different groups and alleles or genotypes of APOE polymorphism was estimated using odds ratios (OR) and 95% confidence intervals (CI). Levels of significance were determined using contingency tables by either Chi-square or Fisher exact analysis using the STATA (v8) software. The analysis of regression and significance of differences for level of cholesterol and TG was established by one-way analysis of variance followed by Dunnett post hoc multiple comparison tests using SPSS software Version 11.5. The significance level was set at 5 percent.


 :: Results Top


We examined the APOE allele frequencies in patients with normal and abnormal total serum cholesterol levels, and observed that the frequency of allele E2 was significantly higher in patients with total serum cholesterol level <200 mg/dl (P 0.01 OR 2.1 95% CI 1.1-4.2). While the frequency of allele E3 was higher in patients with total serum cholesterol level >200 mg/dl it did not reach levels of significance (P 0.05 OR 1.5 95% CI 0.9-2.5). We also observed that the frequency of genotype E2/E3 and E2/E4 was significantly higher in patients with normal total serum cholesterol level compared to patients with abnormal cholesterol (P=0.003 OR 2.4 95% CI; 1.3-4.6). It was still significant after adjustment for sex (OR 2.3 95% CI; 1.3-4.7) and age (OR 1.04 95% CI; 1.02-1.06) [Table 1].
Table 1: APOE allele and genotype frequencies in patients with normal and abnormal total serum cholesterol level

Click here to view


Furthermore, we examined if there was a significant difference for association between APOE gene polymorphisms and normal and abnormal serum cholesterol levels in two groups with BMI<30 or BMI≥30. No significant differences were found (P 0.5) [Table 2].
Table 2: APOE allele frequencies in different groups

Click here to view


Also no significant association between APOE gene polymorphism and mean serum TG levels was found in our population. There was no significant difference for association between APOE gene polymorphism and mean serum TG levels when we compared between different groups with BMI<30 or BMI≥30.


 :: Discussion Top


Genetic variation of APOE is a major determinant of inter-individual variation in susceptibility to dyslipidemia or coronary heart disease (CHD). [10],[11],[12],[13] Kao et al.,[1] first reported APOE polymorphism and its effect on lipid parameters in 546 unrelated Chinese in Taiwan by isoelectric focusing (IEF) and immunoblotting method for APOE phenotyping. It has been suggested that E2/3/4 protein isoforms of APOE are the major causes of lipid and apolipoprotein variability in many populations including Dutch, Nigerian, Japanese and Mexican-American samples. [14],[15],[16],[17]

We observed that the frequency of allele E2 was significantly higher in patients with normal total cholesterol level. Also, the number of individuals carrying allele E2 (genotype E2/E3 and E2/E4) was significantly higher in those with normal total serum cholesterol level compared to patients with abnormal cholesterol. The association between allele E2 and lower total serum cholesterol level was not significantly different when we classified the groups based on BMI. No significant associations between APOE gene polymorphism and serum TG levels were found.

In this study we have found that APO E3 allele in the Iranian population was the most common allele which is in keeping with other reports. [5] However, the frequencies of allele E2 were slightly increased and allele E4 was somewhat decreased in our population compared to the other groups which reported between 0.10 and 0.20 for allele E4 and 0.05 and 0.10 for allele E2 in most Caucasian populations. [5] The association between allele E2 and lower total cholesterol level has been reported in previous studies [4] which has been confirmed in our study. In most reports an association between APOE E4 allele and increased levels of total and LDL serum cholesterol also has been reported [18] which was not found in our population whereas in our population we found an increase in the frequency of allele E3 in individuals with higher total serum cholesterol level, however, it did not reach levels of significance. This might be due to a discrepancy in genetic risk contributing to the serum lipid level in different populations.

APOE polymorphism frequencies vary in different ethnic groups. The E2 allele was found to be completely absent in the Bari and Yucpa Amerindians [18] and Saudis [19] while significantly increased among the Mestizo and Negroid populations in Venezuela. [18] In China, different communities showed different frequencies of APOE alleles. [13],[20] In our study we have found that APOE allele E2 is protective against abnormal total serum cholesterol level in an Iranian population. Data presented in this study needs to be confirmed in a larger population with more detailed information for serum lipid profile including HDL, LDL and their subgroups.


 :: Acknowledgment Top


This study was supported by a grant from the Endocrinology and Metabolism Research Centre (EMRC), Tehran University of Medical Sciences.

 
 :: References Top

1.Kao JT, Tsai KS, Chang CJ, Huang PC. The effects of apolipoprotein E polymorphism on the distribution of lipids and lipoproteins in the Chinese population. Atherosclerosis 1995;114:55-9.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Bradley WA, Gianturco SH. ApoE is necessary and sufficient for the binding of large triglyceride-rich lipoproteins to the LDL receptor; apoB is unnecessary. J Lipid Res 1986;27:40-8.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Mahley RW. Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 1988;240:622-30.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Mahley RW, Rall SC Jr. Apolipoprotein E: Far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000;1:507-37.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Wu K, Bowman R, Welch AA, Luben RN, Wareham N, Khaw KT, et al. Apolipoprotein E polymorphisms, dietary fat and fibre, and serum lipids: The EPIC Norfolk study. Eur Heart J 2007;28:2930-6.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Utermann G. Apolipoprotein E polymorphism in health and disease. Am Heart J 1987;113:433-40.  Back to cited text no. 6  [PUBMED]    
7.Marques-Vidal P, Bongard V, Ruidavets JB, Fauvel J, Hanaire-Broutin H, Perret B, et al. Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on lipids and insulin. Obes Res 2003;11:1200-6.  Back to cited text no. 7  [PUBMED]    
8.Zhang X, Xia G, Mai G. Effects of polymorphism of apolipoprotein E gene on body mass index and plasma lipid levels in obese children. Zhonghua Yu Fang Yi Xue Za Zhi 2001;35:412-4.  Back to cited text no. 8  [PUBMED]    
9.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;43:1657-9.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Wang XL, McCredie RM, Wilcken DE. Polymorphisms of the apolipoprotein E gene and severity of coronary artery disease defined by angiography. Arterioscler Thromb Vasc Biol 1995;15:1030-4.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Lai CL, Liu CK, Lin RT, Tai CT. Association of apolipoprotein E polymorphism with ischemic stroke subtypes in Taiwan. Kaohsiung J Med Sci 2007;23:491-7.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Pei WD, Zhang YH, Sun YH, Gu YC, Wang YF, Zhang CY, et al. Apolipoprotein E polymorphism influences lipid phenotypes in Chinese families with familial combined hyperlipidemia. Circ J 2006;70:1606-10.  Back to cited text no. 12      
13.Yang SL, He BX, Liu HL, He ZY, Zhang H, Luo JP, et al. Apolipoprotein E gene polymorphisms and risk for coronary artery disease in Chinese Xinjiang Uygur and Han population. Chin Med Sci J 2004;19:150-4.  Back to cited text no. 13  [PUBMED]    
14.Isaacs A, Sayed-Tabatabaei FA, Aulchenko YS, Zillikens MC, Sijbrands EJ, Schut AF, et al. Heritabilities, apolipoprotein E, and effects of inbreeding on plasma lipids in a genetically isolated population: The Erasmus Rucphen Family Study. Eur J Epidemiol 2007;22:99-105.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  
15.Kamboh MI, Bunker CH, Aston CE, Nestlerode CS, McAllister AE, Ukoli FA. Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African Blacks. Genet Epidemiol 1999;16:205-22.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Gajra B, Candlish JK, Saha N, Heng CK, Soemantri AG, Tay JS. Influence of polymorphisms for apolipoprotein B (ins/del, Xbal, EcoRI) and apolipoprotein E on serum lipids and apolipoproteins in a Japanese population. Genet Epidemiol 1994;11:19-27.  Back to cited text no. 16  [PUBMED]    
17.Hanis CL, Hewett-Emmett D, Douglas TC, Bertin TK, Schull WJ. Effects of the apolipoprotein E polymorphism on levels of lipids, lipoproteins, and apolipoproteins among Mexican-Americans in Starr County, Texas. Arterioscler Thromb 1991;11:362-70.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Fernandez-Mestre MT, Yehirobi C, Montagnani S, Balbas O, Layrisse Z. Genetic variability of apolipoprotein E in different populations from Venezuela. Dis Markers 2005;21:15-9.  Back to cited text no. 18      
19.Al-Khedhairy AA. Apolipoprotein E polymorphism in Saudis. Mol Biol Rep 2004;31:257-60.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Tang H, Yan X, Hua Y, Wei M, Zhang L, Gao J, et al. Distribution of apoE polymorphism in Chinese Yunnan Dehong Dai ethnic group. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2005;22:224-6.  Back to cited text no. 20  [PUBMED]    



 
 
    Tables

  [Table 1], [Table 2]

This article has been cited by
1 The distribution of apolipoprotein E gene polymorphism in Chinese civil aircrews, and a possible risk factor to their overweight and dyslipidemia is cumulative flight time
Huang, H. and Liu, J. and Feng, Y. and Chen, W.
Clinica Chimica Acta. 2013; 416: 36-40
[Pubmed]
2 The distribution of apolipoprotein E gene polymorphism in Chinese civil aircrews, and a possible risk factor to their overweight and dyslipidemia is cumulative flight time
He Huang,Jing Liu,Yingjin Feng,Weiru Chen
Clinica Chimica Acta. 2013; 416: 36
[Pubmed]
3 Apolipoprotein E gene polymorphism and its effect on anthropometric measures in normoglycemic subjects and type 2 diabetes
Ozra Tabatabaei-Malazy,Hossein Fakhrzadeh,Mostafa Qorbani,Parvin Amiri,Bagher Larijani,Javad Tavakkoly-Bazzaz,Mahsa M Amoli
Journal of Diabetes & Metabolic Disorders. 2012; 11(1): 18
[Pubmed]
4 Modern concepts of gene polymorphisms, which regulate lipid metabolism
Kirillova, O.O.
Voprosy Pitaniia. 2012; 81(4): 48-52
[Pubmed]
5 Diet, genetics, and disease: A focus on the Middle East and North Africa region
Fahed, A.C. and El-Hage-Sleiman, A.-K.M. and Farhat, T.I. and Nemer, G.M.
Journal of Nutrition and Metabolism. 2012; 2012(109037)
[Pubmed]
6 Diet, Genetics, and Disease: A Focus on the Middle East and North Africa Region
Akl C. Fahed,Abdul-Karim M. El-Hage-Sleiman,Theresa I. Farhat,Georges M. Nemer
Journal of Nutrition and Metabolism. 2012; 2012: 1
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Medknow