Abstract
We determined the distribution of the polymorphic variants of CETP TaqIB and ApoE genes and their association with lipid and anthropometric parameters in hyperlipidemic and normolipidemic Asian Indians in North India. CETP TaqIB and ApoE polymorphism were assayed by PCR–RFLP in hyperlipidemic (n = 220) and normolipidemic (n = 367) subjects. Plasma lipids levels were estimated using commercially available kits from Randox (USA). The distribution of CETP TaqIB genotypes and alleles did not differ between the two groups. The frequency of ApoE ε4 allele was significantly higher in hyperlipidemic than normolipidemic subjects. Serum lipid levels were comparable between subjects with the different CETP TaqIB and ApoE genotypes in the two groups. Multivariate analysis after adjusting for age, sex, BMI, WHR, and total skinfold thickness showed that subjects with the Ε3Ε4 genotype and ε4 allele carriers were at significantly higher odds to develop hyperlipidemia [2.07 (1.29–3.30) and 2.05 (1.30–3.24), respectively] as compared to the other genotypes. ApoE ε4 allele and E3E4 genotype emerged as important genetic markers for hyperlipidemia in this study population.
Similar content being viewed by others
Abbreviations
- Apo:
-
Apolipoprotein
- Arg:
-
Arginine
- BMI:
-
Body mass index
- CVD:
-
Cardiovascular disease
- CE:
-
Cholesterol ester
- CAD:
-
Coronary artery disease
- CHD:
-
Coronary heart disease
- CETP:
-
Cholesterol ester transfer protein
- Cys:
-
Cysteine
- dNTP:
-
Deoxynucleoside triphosphate
- DMSO:
-
Dimethylsulphoxide
- EDTA:
-
Ethylene diamine tetra acetic acid
- HDL:
-
High density lipoprotein
- HDL-c:
-
High density lipoprotein cholesterol
- HC:
-
Hip circumference
- IDL:
-
Intermediate density lipoprotein
- LCAT:
-
Lecithin cholesterol acyltransferase
- LDL:
-
Low density lipoprotein
- LDL-c:
-
Low density lipoprotein cholesterol
- LDL-R:
-
Low density lipoprotein-receptor
- LRP:
-
LDL-related protein
- MetS:
-
Metabolic syndrome
- OR:
-
Odds ratio
- PAGE:
-
Polyacrylamide gel electrophoresis
- PCR:
-
Polymerase chain reaction
- PPHL:
-
Postprandial hyperlipidemia
- RCT:
-
Reverse cholesterol transport
- RFLP:
-
Restriction fragment length polymorphism
- SNP:
-
Single nucleotide polymorphism
- SD:
-
Standard deviation
- T2DM:
-
Type 2 diabetes mellitus
- TEMED:
-
N,N,N′,N′-Tetramethyl ethylenediamine
- TC:
-
Total cholesterol
- TG:
-
Triglyceride
- TRL:
-
Triglyceride-rich lipoprotein
- TSF:
-
Total skinfold
- VLDL:
-
Very low density lipoprotein
- VLDL-c:
-
Very low density lipoprotein cholesterol
- WHR:
-
Waist hip ratio
- WC:
-
Waist circumference
References
Tall AR (1993) Plasma cholesteryl ester transfer protein. J Lipid Res 34:1255–1274
Tall AR (1998) An overview of reverse cholesterol transport. Eur Heart J 19(Suppl A):A31–A35
Agellon LB, Quinet EM, Gillette TG, Drayna DT, Brown ML, Tall AR (1990) Organization of the human cholesteryl ester transfer protein gene. Biochemistry 29:1372–1376
de Grooth GJ, Klerkx AH, Stroes ES, Stalenhoef AF, Kastelein JJ, Kuivenhoven JA (2004) A review of CETP and its relation to atherosclerosis. J Lipid Res 45:1967–1974
Kondo I, Berg K, Drayna D, Lawn R (1989) DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels. Clin Genet 35:49–56
Freeman DJ, Packard CJ, Shepherd J, Gaffney D (1990) Polymorphisms in the gene coding for cholesteryl ester transfer protein are related to plasma high-density lipoprotein cholesterol and transfer protein activity. Clin Sci (Lond) 79:575–581
Drayna D, Lawn R (1987) Multiple RFLPs at the human cholesteryl ester transfer protein (CETP) locus. Nucleic Acids Res 15:4698
Mendis S, Shepherd J, Packard CJ, Gaffney D (1990) Genetic variation in the cholesteryl ester transfer protein and apolipoprotein A-I genes and its relation to coronary heart disease in a Sri Lankan population. Atherosclerosis 83:21–27
Kawasaki I, Tahara H, Emoto M, Shoji T, Nishizawa Y (2002) Relationship between TaqIB cholesteryl ester transfer protein gene polymorphism and macrovascular complications in Japanese patients with type 2 diabetes. Diabetes 51:871–874
Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ (1998) The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med 338:86–93
Corbex M, Poirier O, Fumeron F, Betoulle D, Evans A, Ruidavets JB, Arveiler D, Luc G, Tiret L, Cambien F (2000) Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction. Genet Epidemiol 19:64–80
Arca M, Montali A, Ombres D, Battiloro E, Campagna F, Ricci G, Verna R (2001) Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis. Clin Genet 60:374–380
Cuchel M, Wolfe ML, deLemos AS, Rader DJ (2002) The frequency of the cholesteryl ester transfer protein-TaqI B2 allele is lower in African Americans than in Caucasians. Atherosclerosis 163:169–174
Tenkanen H, Koshinen P, Kontula K, Aalto-Setala K, Manttari M, Manninen V, Runeberg SL, Taskinen MR, Ehnholm C (1991) Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease. Hum Genet 87:574–578
Huang Y, Liu XQ, Rall SC Jr, Taylor JM, von Eckardstein A, Assmann G, Mahley RW (1998) Overexpression and accumulation of apolipoprotein E as a cause of hypertriglyceridemia. J Biol Chem 273:26388–26393
von Eckardstein A, Assmann G (1998) High density lipoproteins and reverse cholesterol transport: lessons from mutations. Atherosclerosis 137(Suppl):S7–S11
Scott J, Knott TJ, Shaw DJ, Brook JD (1985) Localization of genes encoding apolipoproteins CI, CII, and E to the p13—cen region of human chromosome 19. Hum Genet 71:144–146
Howard BV, Gidding SS, Liu K (1998) Association of apolipoprotein E phenotype with plasma lipoproteins in African-American and white young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol 148:859–868
Weisgraber KH, Rall SC Jr, Mahley RW (1981) Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J Biol Chem 256:9077–9083
Sing CF, Davignon J (1985) Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 37:268–285
Stengard JH, Kardia SL, Hamon SC, Frikke-Schmidt R, Tybjaerg-Hansen A, Salomaa V, Boerwinkle E, Sing CF (2006) Contribution of regulatory and structural variations in APOE to predicting dyslipidemia. J Lipid Res 47:318–328
Shin MH, Kim HN, Cui LH, Kweon SS, Park KS, Heo H, Nam HS, Jeong SK, Chung EK, Choi JS (2005) The effect of apolipoprotein E polymorphism on lipid levels in Korean adults. J Korean Med Sci 20:361–366
Pitsavos C, Choumerianou DM, Skoumas J, Maumus S, Stefanadis C, Dedoussis GV, Visvikis-Siest S (2005) Apolipoprotein E polymorphism is not associated with lipid levels and coronary artery disease in Greek patients with familial hypercholesterolaemia. Clin Exp Med 5:196–201
Camsari A, Tamer L, Aras Ates N, Pekdemir H, Cicek D, Ercan B, Camdeviren H, Atik U (2005) Apolipoprotein E polymorphism in diabetic and non-diabetic patients: does it really contribute to atherosclerosis? Acta Cardiol 60:409–414
Misra A, Pandey RM, Sharma R (2002) Non-communicable diseases (diabetes, obesity and hyperlipidaemia) in urban slums. Natl Med J India 15:242–244
Misra A, Luthra K, Vikram NK (2004) Dyslipidemia in Asian Indians: determinants and significance. J Assoc Physicians India 52:137–142
Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) (2001) 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 285:2486–2497
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Vikram NK, Misra A, Dwivedi M, Sharma R, Pandey RM, Luthra K, Chatterjee A, Dhingra V, Jailkhani BL, Talwar KK, Guleria R (2003) Correlations of C-reactive protein levels with anthropometric profile, percentage of body fat and lipids in healthy adolescents and young adults in urban North India. Atherosclerosis 168:305–313
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Fumeron F, Rigaud D, Bertiere MC, Bardon S, Dely C, Apfelbaum M (1988) Association of apolipoprotein epsilon 4 allele with hypertriglyceridemia in obesity. Clin Genet 34:258–264
Kim YS, Paeng JR, Woo JT, Kim SW, Yang IM, Kim JW, Kim KW, Choi YK (1993) Apolipoprotein E genotypes of normal and hyperlipidemic subjects. J Korean Med Sci 8:262–266
Singh PP, Singh M, Bhatnagar DP, Kaur TP, Gaur SK (2008) Apolipoprotein E polymorphism and its relation to plasma lipids in coronary heart disease. Indian J Med Sci 62:105–112
Bahri R, Esteban E, Moral P, Hassine M, Ben Hamda K, Chaabani H (2008) Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease. Lipids Health Dis 7:46
Stancakova A, Baldaufova L, Javorsky M, Kozarova M, Salagovic J, Tkac I (2006) Effect of gene polymorphisms on lipoprotein levels in patients with dyslipidemia of metabolic syndrome. Physiol Res 55:483–490
Padmaja N, Ravindra Kumar M, Soya SS, Adithan C (2007) Common variants of Cholesteryl ester transfer protein gene and their association with lipid parameters in healthy volunteers of Tamilian population. Clin Chim Acta 375:140–146
Hassanzadeh T, Firoozrai M, Zonouz AE, Zavarehee A, Paoli M (2009) Taq1B polymorphism of cholesteryl ester transfer protein (CETP) gene in primary combined hyperlipidaemia. Indian J Med Res 129:293–298
Relvas WG, Izar MC, Helfenstein T, Fonseca MI, Colovati M, Oliveira A, Ihara SS, Han SW, Las Casas AA Jr, Fonseca FA (2005) Relationship between gene polymorphisms and prevalence of myocardial infarction among diabetic and non-diabetic subjects. Atherosclerosis 178:101–105
Zheng KQ, Zhang SZ, He Y, Zhang L, Zhang KL, Huang DJ, Sun Y (2004) Association between cholesteryl ester transfer protein gene polymorphisms and variations in lipid levels in patients with coronary heart disease. Chin Med J (Engl) 117:1288–1292
Jensen MK, Mukamal KJ, Overvad K, Rimm EB (2008) Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein, high-density lipoprotein cholesterol, and risk of coronary heart disease in men and women. Eur Heart J 29:104–112
McCaskie PA, Beilby JP, Chapman CM, Hung J, McQuillan BM, Thompson PL, Palmer LJ (2007) Cholesteryl ester transfer protein gene haplotypes, plasma high-density lipoprotein levels and the risk of coronary heart disease. Hum Genet 121:401–411
Meena K, Misra A, Panday RM, Luthra K (2007) CETP TaqIB polymorphisms and CETP activity in normolipidemic healthy northern Indians. Diabetes Metab Syndr 1:239–244
Acknowledgment
This work was funded by the Indian Council of Medical Research (Ref: No. 53/14/2003-BMS), New Delhi, India.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Meena, K., Misra, A., Vikram, N. et al. Cholesterol ester transfer protein and apolipoprotein E gene polymorphisms in hyperlipidemic Asian Indians in North India. Mol Cell Biochem 352, 189–196 (2011). https://doi.org/10.1007/s11010-011-0753-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-011-0753-1