Abstract
Type 2 diabetes mellitus is a metabolic, vascular, and neuropathic disease with a high risk of atherosclerotic events due to dyslipidemic states. Polymorphisms in Apolipoprotein A5 gene (APOA5) have been associated with increased triglyceride levels in many different populations. This study aimed to identify the frequencies of the APOA5 −1131T>C and SW19 polymorphisms and evaluate their effects on lipid levels in patients with type 2 diabetes. Genotyping of APOA5 −1131T>C and SW19 polymorphisms was performed by PCR–RFLP in 146 diabetic patients and in controls (n = 173), from 30 to 80 years of age. Diabetic patients were divided into two groups: patients not treated with lipid lowering drugs (group G1; n = 62) and those treated with lipid lowering drugs (group G2, n = 84). Lipids and lipoproteins were determined enzymatically. Among participants not treated with lipid-lowering drugs (diabetics G1 and controls; n = 235), the −1131C was associated with lower LDLc levels (p = 0.015). In the diabetic patients, the 19W allele was associated with higher triglyceride levels (p = 0.004). In G1 diabetic patients, the combined analysis of APOA5 −1131T>C and SW19 polymorphisms showed that [TC or CC] + SS carriers presented lower total cholesterol levels than did other genotype combinations (p = 0.049). It could therefore be concluded that APOA5 −1131T>C and SW19 polymorphisms influence lipid levels in type 2 diabetic patients.
Similar content being viewed by others
References
American Heart Association NCEP (2004) Report implications of recent clinical trials for the national cholesterol education program adult treatment panel III. Circulation 110:227–239
Baigent C, Keech A, Kearney PM et al (2005) Cholesterol treatment trialist’s (C-FF) collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomized trials of statins. Lancet 366:267–278
Mendes-Lana A, Pena GG, Freitas SN et al (2007) Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto Study. Braz J Med Biol Res 40:49–56
Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173
van der Vliet HN, Sammels MG, Leegwater AC et al (2001) Apolipoprotein AV: A novel apolipoprotein associated with an early phase of liver regeneration. J Biol Chem 276:44512–44520
Horinek A, Vrablik M, Ceska R, Adamkova V, Poledne R, Hubacek JA (2003) 1131T>C polymorphism within the apolipoprotein AV gene in hypertriglyceridemic individuals. Atherosclerosis 167:369–370
Merkel M, Heeren J (2005) Give me A5 for lipoprotein hydrolysis! J Clin Invest 115:2694–2696
Ribalta J, Figuera L, Fernandez-Ballart J et al (2002) Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides in familial combined hyperlipidemia. Clin Chem 48:1597–1600
Evans D, Buchwald A, Beil Fu (2003) The single nucleotide polymorphism −1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipemia. J Mol Med 81:645–654
Moreno-Luna R, Perez-Jimenez F, Marin C et al (2007) Two independent apolipoprotein A5 haplotypes module post-prandial lipoprotein metabolism in a healthy Caucasian population. J Endocrin Metab 92:2280–2285
Pennacchio LA, Olivier M, Hubacek RM et al (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038
Pennacchio LA, Rubin EM (2003) Apolipoprotein A5, a newly identified agent that affects plasma triglyceride levels in humans and mice. Arteriosclerosis 23:529–534
Martinelli N, Trabetti E, Bassi A et al (2007) The −1131T>C and SW19 APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease. Atherosclerosis 191:409–417
Charriere S, Bernard S, Aqallal M et al (2008) Association of APOA5 −1131T>C and S19W gene polymorphisms with both mild hypertriglyceridemia and hyperchylomicronemia in type 2 diabetic patients. Clin Chim Acta 394:99–103
Liu H, Zhang S, Lin J et al (2005) Association between DNA variants sites in the apolipoprotein A5 gene and coronary heart disease in Chinese. Metabolism 54:568–572
Brazilian Society of Cardiology (2007) IV Brazilian guidelines on dyslipidemia and guideline of atherosclerosis prevention. Arq Bras Cardiol 88:1– 19, suppl. I
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Sousa MO, Alía P, Pintó X, Corbella E, Navarro MA (2008) Interaction between APOA5 −1131T>C and APOE polymorphisms and their association with severe hypertriglyceridemia. Clin Chim Acta 395:68–71
Brito DD, Fernandes AP, Gomes KB et al (2010) Apolipoprotein A5 −1131T>C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents. Mol Biol Rep 38:4381-4388
De Andrade FM, Maluf SW, Schuch JB et al. (2011) The influence of the S19W SNP of the APOA5 gene on triglyceride levels in southern Brazil: Interactions with the APOE gene, sex and menopause status. Nutr Metab Cardiovasc Dis 21:548–590
Brazilian Society of Cardiology (2001) III Brazilian guidelines on dyslipidemia and guideline of atherosclerosis prevention. N Engl J Med 77:1– 48, suppl. III
Lazar MA (2005) How obesity causes diabetes: not a tall tale. Science 307:373–375
Yologlu S, Sezgin AT, Sezgin N, Ozdemir R, Yesilada E, Topal E (2005) Determination of risk factors in obese and non-obese patients with coronary artery disease. Acta Cardiol 60:625–629
Gomes MB, Neto DG, Mendonça E, Tambasco MA, Fonseca RM, Rea RR (2006) Prevalence of overweight and obesity in patients with type 2 diabetes mellitus in Brazil: national multicenter study. Arq Bras Endocrinol Metab 50:136–144
Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SDJ (2003) Color and genomic ancestry in Brazilians. Proc Natl Acad Sci USA 100:177– 182
Prochaska CL, Picheth G, Anghebem-Oliveira MI et al (2010) The polymorphisms −1131T>C and the SW19 of the APOA5 gene are not associated with coronary artery disease in the Brazilian population. Clin Chem Lab Med 48:419–422
Szalai C, Keszei M, Duba J et al (2004) Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease. Atherosclerosis 173:109–114
Nabika T, Nasreen S, Kobayashi et al (2002) The genetic effect of apolipoprotein AV gene on the serum triglyceride level in Japanese. Atherosclerosis 165:201–204
Jang Y, Paik JK, Hyun JY et al (2009) The apolipoprotein A5–1131T>C promoter polymorphism in Koreans: association with plasma serum triglyceride concentrations, LDL particle size and coronary artery disease. Chin Chim Acta 402:83–87
Evans D, Buchwald A, Beil FU (2003) The single nucleotide polymorphism −1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides levels in patients with hyperlipidemia. J Mol Med 81:645–654
Charriere S, Bernard S, Aqallal M et al (2008) Association of APOA5 −1131T>C and S19W gene polymorphisms with both mild hypertriglyceridemia and hyperchylomicronemia in type 2 diabetic patients. Clin Chim Acta 394:99–103
Hsu L, Yu LK, Chang CJ (2006) Genetic variations of apolipoprotein A5 gene are associated with the risk of coronary artery disease among Chineses in Taiwan. Atherosclerosis 185:143–149
Liu H, Zhang S, Lin J et al (2005) Association between DNA variants sites in the apolipoprotein A5 gene and coronary heart disease in Chinese. Metabolism 54:568–572
Nilsson SK, Lookene A, Beckstead JA (2007) Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family. Biochemistry 46:3896–3904
Talmud PJ, Hawe E, Martin S et al (2002) Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 11:3039–3046
Qi L, Liu S, Rifai N, Hunter D, Hu FB (2007) Associations of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride and HDL cholesterol levels in women with type 2 diabetes. Atherosclerosis 192:204–210
Dorfmeister B, Cooper JA, Stephens JW et al (2007) The effect of APOA5 and APOAC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes. Biochim Biophys Acta 1772:355–356
Acknowledgments
We acknowledge the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado Minas Gerais (FAPEMIG) and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais (UFMG) for financial support. We thank Fátima, Márcio and Eunice (Department of Clinical and Toxicological Analysis of the Faculty of Pharmacy of UFMG). Most of all, thanks to all patients and healthy volunteers for their selfless donation of samples used in this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sóter, M.O., Gomes, K.B., Fernandes, A.P. et al. −1131T>C and SW19 polymorphisms in APOA5 gene and lipid levels in type 2 diabetic patients. Mol Biol Rep 39, 7541–7548 (2012). https://doi.org/10.1007/s11033-012-1588-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-012-1588-x