APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals
-
Simone C. Sorkin
Abstract
Background: Apolipoprotein A-I gene (APOA1) polymorphisms have been associated with variations in serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol. We have investigated whether APOA1 common variants are also associated with variations in basal triglyceride serum concentrations and response to atorvastatin in individuals with hypercholesterolemia.
Methods: APOA1 G–75A and C83T polymorphisms and variations in serum lipids were evaluated in 150 hypercholesterolemic (HC) and 93 normolipidemic (NL) unrelated European-derived Brazilians treated with atorvastatin (10mg/day for 4weeks). Genomic DNA was extracted from blood leukocytes using a salting-out method and APOA1 polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism.
Results: G–75A polymorphism was associated with differences in serum concentrations of triglyceride and very low-density lipoprotein (VLDL)-cholesterol (p=0.026) in HC men. After atorvastatin treatment, women carrying the GG/CC haplotype had lower serum triglyceride and VLDL-cholesterol (p=0.020) than non-carriers. In men, the reduction in serum triglyceride in response to atorvastatin was found to be slightly lower in GG/CC haplotype carriers (p=0.051).
Conclusion: Our data suggest that APOA1 polymorphisms are associated with variations of baseline serum concentrations of triglyceride and VLDL-cholesterol and in response to atorvastatin in a gender-specific manner.
References
1. Segrest JP, Li L, Anantharamaiah GM, Harvey SC, Liadaki KN, Zannis V. Structure and function of apolipoprotein A-I and high-density lipoprotein. Curr Opin Lipidol 2000; 11:105–15.10.1097/00041433-200004000-00002Search in Google Scholar
2. Stein O, Stein Y. Atheroprotective mechanisms of HDL. Atherosclerosis 1999; 144:285–301.10.1016/S0021-9150(99)00065-9Search in Google Scholar
3. Groenendijk M, Cantor RM, de Bruin TW, Dallinga-Thie GM. The apoAI-CIII-AIV gene cluster. Atherosclerosis 2001; 157:1–11.10.1016/S0021-9150(01)00539-1Search in Google Scholar
4. Jeenah M, Kessling A, Miller N, Humphries SE. G to A substitution in the promoter region of the apolipoprotein A gene is associated with elevated serum apolipoprotein A-I and high density lipoprotein cholesterol concentrations. Mol Biol Med 1990; 7:233–41.Search in Google Scholar
5. Pagani F, Sidoli A, Giudici GA, Barenghi L, Vergani C, Baralle FE. Human apolipoprotein A-I gene promoter polymorphism: association with hyperalphalipoproteinemia. J Lipid Res 1990; 31:1371–7.10.1016/S0022-2275(20)42608-2Search in Google Scholar
6. Wang XL, Badenhop R, Humphrey KE, Wilcken DE. C to T and/or G to A transitions are responsible for loss of a MspI restriction site at the 5′-end of the human apolipoprotein AI gene. Hum Genet 1995; 95:473–4.10.1007/BF00208984Search in Google Scholar
7. Paul-Hayase H, Rosseneu M, Robinson D, Van Bervliet JP, Deslypere JP, Humphries SE. Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apoAI, apoCIII and apoAIV concentrations. Hum Genet 1992; 88:439–46.10.1007/BF00215679Search in Google Scholar
8. Sigurdsson G Jr, Gudnason V, Sigurdsson G, Humphries SE. Interaction between a polymorphism of the apo A-I promoter region and smoking determines plasma concentrations of HDL and apo A-I. Arterioscler Thromb 1992; 12:1017–22.10.1161/01.ATV.12.9.1017Search in Google Scholar
9. Saha N, Tay JS, Low PS, Humphries SE. Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in Chinese non-smokers. Genet Epidemiol 1994; 11:255–64.10.1002/gepi.1370110304Search in Google Scholar
10. Talmud PJ, Ye S, Humphries SE. Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: the European Atherosclerosis Research Study. Genet Epidemiol 1994; 11:265–80.10.1002/gepi.1370110305Search in Google Scholar
11. Kamboh MI, Aston CE, Nestlerode CM, McAllister AE, Hamman RF. Haplotype analysis of two APOAI/MspI polymorphisms in relation to plasma levels of Apo A-I and HDL-cholesterol. Atherosclerosis 1996; 127:255–62.10.1016/S0021-9150(96)05966-7Search in Google Scholar
12. Civeira F, Pocovi M, Cenarro A, Garces C, Ordovas JM. Adenine for guanine substitution −78 base pairs 5′ to the apolipoprotein (APO) A-I gene: relation with high density lipoprotein cholesterol and APO A-I concentrations. Clin Genet 1993; 44:307–12.10.1111/j.1399-0004.1993.tb03906.xSearch in Google Scholar
13. Barre DE, Guerra R, Verstraete R, Wang Z, Grundy SM, Cohen JC. Genetic analysis of a polymorphism in the human apolipoprotein A-I gene promoter: effect on plasma HDL-cholesterol levels. J Lipid Res 1994; 35:1292–6.10.1016/S0022-2275(20)39972-7Search in Google Scholar
14. Peacock RE, Hamsten A, Johansson J, Nilsson-Ehle P, Humphries SE. Associations of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses. Clin Genet 1994; 46:273–82.10.1111/j.1399-0004.1994.tb04159.xSearch in Google Scholar
15. Akita H, Chiba H, Tsuji M, Hui SP, Takahashi Y, Matsuno K, et al. Evaluation of G-to-A substitution in the apolipoprotein A-I gene promoter as a determinant of high-density lipoprotein cholesterol level in subjects with and without cholesteryl ester transfer protein deficiency. Hum Genet 1995; 96:521–6.10.1007/BF00197405Search in Google Scholar
16. Minnich A, DeLangavant G, Lavigne J, Roederer G, Lussier-Cacan S, Davignon J. G→A substitution at position −75 of the apolipoprotein A-I gene promoter. Evidence against a direct effect on HDL cholesterol levels. Arterioscler Thromb Vasc Biol 1995; 15:1740–5.10.1161/01.ATV.15.10.1740Search in Google Scholar
17. Kamboh MI, Bunker CH, Aston CE, Nestlerode CS, McAllister AE, Ukoli FA. Genetic association of five polymorphisms with serum lipoprotein lipid levels in African Blacks. Genet Epidemiol 1999; 16:205–22.10.1002/(SICI)1098-2272(1999)16:2<205::AID-GEPI7>3.0.CO;2-PSearch in Google Scholar
18. Juo SH, Wyszynski DF, Beaty TH, Huang HY, Bailey-Wilson JE. Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis. Am J Med Genet 1999; 29:82:235–41.10.1002/(SICI)1096-8628(19990129)82:3<235::AID-AJMG8>3.0.CO;2-HSearch in Google Scholar
19. Wang XL, Badenhop R, Humphrey KE, Wilcken DE. New MspI polymorphism at +83 bp of the human apolipoprotein AI gene: association with increased circulating high density lipoprotein cholesterol levels. Genet Epidemiol 1996; 13:1–10.10.1002/(SICI)1098-2272(1996)13:1<1::AID-GEPI1>3.0.CO;2-DSearch in Google Scholar
20. Pulkkinen A, Viitanen L, Kareinen A, Lehto S, Laakso M. MspI polymorphism at +83 bp in intron 1 of the human apolipoprotein A1 gene is associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease. Diabetes Care 2000; 23:791–5.10.2337/diacare.23.6.791Search in Google Scholar
21. Zou Y, Hu D, Yang X, Jia X, Wang L, Cui L, et al. Relationships among apolipoprotein A1 gene polymorphisms, lipid levels and coronary atherosclerosis disease. Chin Med J 2003; 116:665–8.Search in Google Scholar
22. Ma YQ, Thomas GN, Ng MC, Critchley JA, Cockram CS, Chan JC, et al. Association of two apolipoprotein A-I gene MspI polymorphisms with high density lipoprotein (HDL)-cholesterol levels and indices of obesity in selected healthy Chinese subjects and in patients with early-onset type 2 diabetes. Clin Endocrinol (Oxf) 2003; 59:442–9.10.1046/j.1365-2265.2003.01865.xSearch in Google Scholar
23. Reguero JR, Cubero GI, Batalla A, Alvarez V, Hevia S, Cortina A, et al. Apolipoprotein A1 gene polymorphisms and risk of early coronary disease. Cardiology 1998; 90:231–5.10.1159/000006849Search in Google Scholar
24. Wang XL, Liu SX, McCredie RM, Wilcken DE. Polymorphisms at the 5′-end of the apolipoprotein AI gene and severity of coronary artery disease. J Clin Invest 1996; 98:372–77.10.1172/JCI118802Search in Google Scholar
25. Edwards JE, Moore RA. Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomized, double blind trials. BMC Fam Pract 2003; 1:4–18.Search in Google Scholar
26. Wang M, Briggs MR. HDL: the metabolism, function, and therapeutic importance. Chem Rev 2004; 104:119–37.10.1021/cr020466vSearch in Google Scholar
27. Rader DJ. Regulation of reverse cholesterol transport and clinical implications. Am J Cardiol 2003; 92:42J–9J.10.1016/S0002-9149(03)00615-5Search in Google Scholar
28. Lahoz C, Pena R, Mostaza JM, Jimenez J, Subirats E, Pinto X, et al. Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy. Atherosclerosis 2003; 168:289–95.10.1016/S0021-9150(03)00094-7Search in Google Scholar
29. Mata P, Lopez-Miranda J, Pocovi M, Alonso R, Lahoz C, Marin C, et al. Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation. Atherosclerosis 1998; 137:367–76.10.1016/S0021-9150(97)00265-7Search in Google Scholar
30. Dallinga-Thie GM, Bu XD, van Linde-Sibenius Trip M, Rotter JI, Lusis AJ, de Bruin TW. Apolipoprotein A-I/C-III/A-IV gene cluster in familial combined hyperlipidemia: effects on LDL-cholesterol and apolipoproteins B and C-III. J Lipid Res 1996; 37:136–47.10.1016/S0022-2275(20)37642-2Search in Google Scholar
31. Dallinga-Thie GM, van Linde-Sibenius Trip M, Rotter JI, Cantor RM, Bu X, Lusis AJ, et al. Complex genetic contribution of the Apo AI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes. J Clin Invest 1997; 99:953–61.10.1172/JCI119260Search in Google Scholar
32. Grundy SM. United States Cholesterol Guidelines 2001: expanded scope of intensive low-density lipoprotein-lowering therapy. Am J Cardiol 2001; 88:23J–7J.10.1016/S0002-9149(01)01931-2Search in Google Scholar
33. Bae CY, Keenan JM, Wenz J, McCaffrey DJ. A clinical trial of the American Heart Association step one diet for treatment of hypercholesterolemia. J Farm Pract 1991; 33:249–54.Search in Google Scholar
34. Dobiasova M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FERHDL). Clin Biochem 2001; 34:583–8.10.1016/S0009-9120(01)00263-6Search in Google Scholar
35. Salazar LA, Hirata, MH, Cavalli SA, Machado MO, Hirata RD. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem 1998; 44:1748–50.10.1093/clinchem/44.8.1748Search in Google Scholar
36. Larson IA, Ordovas JM, Barnard JR, Hoffmann MM, Feussner G, Lamon-Fava S, et al. Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein, serum lipoprotein and glucose levels. Clin Genet 2002; 61:176–84.10.1034/j.1399-0004.2002.610302.xSearch in Google Scholar
37. Gonzalez-Amieva A, Lopez-Miranda J, Marin C, Perez-Martinez P, Gomez P, Paz-Rojas E, et al. The apo A-I gene promoter region polymorphism determines the severity of hyperlipidemia after heart transplantation. Clin Transplant 2003; 17:56–62.10.1034/j.1399-0012.2003.02038.xSearch in Google Scholar
38. Souverein OW, Jukema JW, Boekholdt SM, Zwinderman AH, Tanck MW. Polymorphisms in APOA1 and LPL genes are statistically independently associated with fasting TG in men with CAD. Eur J Hum Genet 2005; 13:445–51.10.1038/sj.ejhg.5201362Search in Google Scholar
39. Angotti E, Mele E, Costanzo F, Avvedimento EV. A polymorphism (G→A transition) in the −78 position of the apolipoprotein A-I promoter increases transcription efficiency. J Biol Chem 1994; 269:17371–4.10.1016/S0021-9258(17)32445-6Search in Google Scholar
40. Wang XL, Badenhop RB, Sim AS, Wilcken DE. The effect on transcription efficiency of the apolipoprotein AI gene of DNA variants at the 5′ untranslated region. Int J Clin Lab Res 1998; 28:235–41.10.1007/s005990050051Search in Google Scholar
41. Groenendijk M, Cantor RM, de Bruin TW, Dallinga-Thie GM. New genetic variants in the apoA-I and apoC-III genes and familial combined hyperlipidemia. J Lipid Res 2001; 42:188–94.10.1016/S0022-2275(20)31678-3Search in Google Scholar
42. Tybjaerg-Hansen A, Nordestgaard BG, Gerdes LU, Faergeman O, Humphries SE. Genetic markers in the apo AI-CIII-AIV gene cluster for combined hyperlipidemia, hypertriglyceridemia, and predisposition to atherosclerosis. Atherosclerosis 1993; 100:157–69.10.1016/0021-9150(93)90202-6Search in Google Scholar
43. Mar R, Pajukanta P, Allayee H, Groenendijk M, Dallinga-Thie G, Krauss RM, et al. Association of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia. Circ Res 2004; 94:993–9.10.1161/01.RES.0000124922.61830.F0Search in Google Scholar PubMed
44. Izar MC, Fonseca FA, Ihara SS, Kasinski N, Sang WH, Lopes IE, et al. Risk factors, biochemical markers, and genetic polymorphisms in early coronary artery disease. Arq Bras Cardiol 2003; 80:379–95.10.1590/S0066-782X2003000400003Search in Google Scholar
45. Lopez-Miranda J, Ordovas JM, Espino A, Marin C, Salas J, Lopez-Segura F, et al. Influence of mutation in human apolipoprotein A-1 gene promoter on plasma LDL cholesterol response to dietary fat. Lancet 1994; 343:1246–9.10.1016/S0140-6736(94)92149-0Search in Google Scholar
46. De Oliveira e Silva ER, Kong M, Han Z, Starr C, Kass EM, Juo SH, et al. Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females. J Lipid Res 1999; 40:1211–21.10.1016/S0022-2275(20)33483-0Search in Google Scholar
47. Ordovas JM, Corella D, Cupples LA, Demissie S, Kelleher A, Coltell O, et al. Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am J Clin Nutr 2002; 75:38–46.10.1093/ajcn/75.1.38Search in Google Scholar
48. Motohashi Y, Maruyama T, Murata M, Nakano S, Maruyama C, Kyotani S, et al. Role of genetic factors (CETP gene Taq I B polymorphism and Apo A-I gene Msp I polymorphism) in serum HDL-C levels in women. Nutr Metab Cardiovasc Dis 2004; 14:6–14.10.1016/S0939-4753(04)80041-3Search in Google Scholar
49. Kajinami K, Brousseau ME, Lamon-Fava S, Ordovas JM, Schaefer EJ. Gender-specific effects of estrogen receptor alpha gene haplotype on high-density lipoprotein cholesterol response to atorvastatin: interaction with apolipoprotein AI gene polymorphism. Atherosclerosis 2005; 178:331–8.10.1016/j.atherosclerosis.2004.08.034Search in Google Scholar PubMed
50. Lennernas H. Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet 2003; 42:1141–60.10.2165/00003088-200342130-00005Search in Google Scholar PubMed
51. van Dijk KW, Rensen PC, Voshol PJ, Havekes LM. The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol 2004; 15:239–46.10.1097/00041433-200406000-00002Search in Google Scholar PubMed
52. Caslake MJ, Packard CJ. Phenotypes, genotypes and response to statin therapy. Curr Opin Lipidol 2004; 15:387–92.10.1097/01.mol.0000137225.46654.4dSearch in Google Scholar PubMed
©2005 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Contents Volume 43, 2005
- Author Index
- Subject Index
- ProteinChips: the essential tools for proteomic biomarker discovery and future clinical diagnostics
- Protein profiling as a diagnostic tool in clinical chemistry: a review
- Protein biochip systems for the clinical laboratory
- Automation of biochip array technology for quality results
- SELDI-TOF-MS proteomics of breast cancer
- Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development
- Separation of human serum proteins using the Beckman-Coulter PF2D™ system: analysis of ion exchange-based first dimension chromatography
- Rapid, accurate genotyping of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 based on the use of denaturing HPLC
- APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals
- Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus
- Glycogen phosphorylase BB in acute coronary syndromes
- Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats
- Glycemic control in diabetes in three Danish counties
- Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells
- Buprenorphine detection in biological samples
- The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population
- High-affinity antibodies in a new immunoassay for plasma tissue factor: reduction in apparent intra-individual variation
- Physiological matrix metalloproteinase concentrations in serum during childhood and adolescence, using Luminex® Multiplex technology
- Sensitive immunoassays for the autoantibodies reacting against citrullinated carboxy-terminal telopeptides of type I and type II collagens in patients with rheumatoid arthritis
- Acknowledgement
Articles in the same Issue
- Contents Volume 43, 2005
- Author Index
- Subject Index
- ProteinChips: the essential tools for proteomic biomarker discovery and future clinical diagnostics
- Protein profiling as a diagnostic tool in clinical chemistry: a review
- Protein biochip systems for the clinical laboratory
- Automation of biochip array technology for quality results
- SELDI-TOF-MS proteomics of breast cancer
- Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development
- Separation of human serum proteins using the Beckman-Coulter PF2D™ system: analysis of ion exchange-based first dimension chromatography
- Rapid, accurate genotyping of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 based on the use of denaturing HPLC
- APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals
- Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus
- Glycogen phosphorylase BB in acute coronary syndromes
- Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats
- Glycemic control in diabetes in three Danish counties
- Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells
- Buprenorphine detection in biological samples
- The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population
- High-affinity antibodies in a new immunoassay for plasma tissue factor: reduction in apparent intra-individual variation
- Physiological matrix metalloproteinase concentrations in serum during childhood and adolescence, using Luminex® Multiplex technology
- Sensitive immunoassays for the autoantibodies reacting against citrullinated carboxy-terminal telopeptides of type I and type II collagens in patients with rheumatoid arthritis
- Acknowledgement