ApoE Polymorphism May Determine Low-Density Lipoprotein Cholesterol Level in Association with Obesity and Metabolic Syndrome in Postmenopausal Korean Women
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: We investigated how serum low-density lipoprotein (LDL) level is related to various isoforms of apolipoprotein (ApoE) polymorphism in association with obesity and metabolic syndrome. Materials and Methods: We gathered total 332 sample of postmenopausal Korean women and analyzed ApoE isoforms, serum lipid level including LDL, blood pressure, fasting glucose, and anthropometry. The relationship between ApoE isoforms and serum lipid level, metabolic syndrome, and obesity was investigated. Results: Six ApoE isoforms were found, ApoE2 [E2/2 (n=1), E2/3 (n=54), E2/4 (n=14)], ApoE3 (E3/3, n=200), ApoE4 [E3/4 (n=55), and E4/4 (n=8)]. The prevalence of metabolic syndrome and obesity showed higher ApoE3 isoform than that of other isoforms. In additon, ApoE3 isoform was related to higher serum LDL and total cholesterol level than to ApoE2 isoform. The odds ratio of having the highest LDL cholesterol quartile in ApoE3 with obesity, compared to ApoE2 without obesity, was 3.46 [95% confidence interval (CI); 1.07-11.14, p=0.037], and odds ratio of ApoE3 with metabolic syndrome compared to ApoE2 without metabolic syndrome was 5.06 (95% CI; 1.14-22.29, p=0.037). Serum LDL cholesterol was positively associated with obesity or metabolic syndrome in ApoE3 isoform. Conclusion: This study suggests that obesity or metabolic syndrome risk should be effectively managed in ApoE3 isomform groups to reduce serum LDL in postmenopausal Korean women.
Abstract
Purpose: We investigated how serum low-density lipoprotein (LDL) level is related to various isoforms of apolipoprotein (ApoE) polymorphism in association with obesity and metabolic syndrome. Materials and Methods: We gathered total 332 sample of postmenopausal Korean women and analyzed ApoE isoforms, serum lipid level including LDL, blood pressure, fasting glucose, and anthropometry. The relationship between ApoE isoforms and serum lipid level, metabolic syndrome, and obesity was investigated. Results: Six ApoE isoforms were found, ApoE2 [E2/2 (n=1), E2/3 (n=54), E2/4 (n=14)], ApoE3 (E3/3, n=200), ApoE4 [E3/4 (n=55), and E4/4 (n=8)]. The prevalence of metabolic syndrome and obesity showed higher ApoE3 isoform than that of other isoforms. In additon, ApoE3 isoform was related to higher serum LDL and total cholesterol level than to ApoE2 isoform. The odds ratio of having the highest LDL cholesterol quartile in ApoE3 with obesity, compared to ApoE2 without obesity, was 3.46 [95% confidence interval (CI); 1.07-11.14, p=0.037], and odds ratio of ApoE3 with metabolic syndrome compared to ApoE2 without metabolic syndrome was 5.06 (95% CI; 1.14-22.29, p=0.037). Serum LDL cholesterol was positively associated with obesity or metabolic syndrome in ApoE3 isoform. Conclusion: This study suggests that obesity or metabolic syndrome risk should be effectively managed in ApoE3 isomform groups to reduce serum LDL in postmenopausal Korean women.
참고문헌 (31)
- Mahley RW, "cholesterol transport protein with expanding role in cell biology", Science, 240, pp.622~630 (1988)
- Weisgraber KH, "structure-function relationships", Adv Protein Chem, 45, pp.249~302 (1994)
- Weisgraber KH, "apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms", J Biol Chem, 256, pp.9077~9083 (1981)
- Mahley RW, "Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes", J Lipid Res, 40, pp.1933~1949 (1999)
- Garg A, "Lipodystrophies", Am J Med, 108, pp.143~152 (2000)
- Haslam DW, "Obesity", Lancet, 366, pp.1197~1209 (2005)
- Zechner R, "Apolipoprotein E gene expression in mouse 3T3-L1 adipocytes and human adipose tissue and its regulation by differentiation and lipid content", J Biol Chem, 266, pp.10583~10588 (1991)
- Elosua R, "Obesity modulates the association among APOE genotype, insulin, and glucose in men", Obes Res, 11, pp.1502~1508 (2003)
- Volcik KA, "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, 164, pp.342~348 (2006)
- Feitosa MF, "Pleiotropic QTL on chromosome 19q13 for triglycerides and adiposity: the HERITAGE Family Study", Atherosclerosis, 185, pp.426~432 (2006)
- Wilson PW, "Apolipoprotein E alleles and risk of coronary disease. A meta-analysis", Arterioscler Thromb Vasc Biol, 16, pp.1250~1255 (1996)
- Bennet AM, "Association of apolipoprotein E genotypes with lipid levels and coronary risk", JAMA, 298, pp.1300~1311 (2007)
- Zintzaras E, "APOE gene polymorphisms and response to statin therapy", Pharmacogenomics J, 9, pp.248~257 (2009)
- Nieminen T, "Pharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: lipid levels and prevention of coronary heart disease", Pharmacogenomics, 9, pp.1475~1486 (2008)
- Miller SA, "A simple salting out procedure for extracting DNA from human nucleated cells", Nucleic Acids Res, 16, pp.1215~ (1988)
- Hixson JE, "Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI", J Lipid Res, 31, pp.545~548 (1990)
- "The cutoff points of waist circumference for abdominal obesity", Korean Society for the Study of Obesity, 15, pp.1~9 (2006)
- "The Asia-Pacific perspective: redefining obesity and its treatment", 2000 Feb. Sponsored by the Regional Office for the Western Pacific WPRO), World Health Organization, the International Association for the Study of Obesity, and the International Obesity Task Force, International Diabetes Institute
- Lamarche B, "The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, patho-physiology and therapeutic aspects", Diabetes Metab, 25, pp.199~211 (1999)
- Lamarche B, "Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study", Circulation, 95, pp.69~75 (1997)
- Ho RC, "Whole-body insulin sensitivity, low-density lipoprotein (LDL) particle size, and oxidized LDL in overweight, nondiabetic men", Metabolism, 51, pp.1478~1483 (2002)
- Goff DC Jr, "Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study", Metabolism, 54, pp.264~270 (2005)
- Chiba T, "VLDL induces adipocyte differentiation in ApoE-dependent manner", Arterioscler Thromb Vasc Biol, 23, pp.1423~1429 (2003)
- Huang ZH, "Endogenous ApoE expression modulates adipocyte triglyceride content and turnover", Diabetes, 55, pp.3394~3402 (2006)
- Gao J, "Involvement of apolipoprotein E in excess fat accumulation and insulin resistance", Diabetes, 56, pp.24~33 (2007)
- Sima A, "Apolipoprotein E polymorphism--a risk factor for metabolic syndrome", Clin Chem Lab Med, 45, pp.1149~1153 (2007)
- Knouff C, "Apo E structure determines VLDL clearance and atherosclerosis risk in mice", J Clin Invest, 103, pp.1579~1586 (1999)
- Michikawa M, "Apolipoprotein E exhibits isoform-specific promotion of lipid efflux from astrocytes and neurons in culture", J Neurochem, 74, pp.1008~1016 (2000)
- Lucic D, "Regulation of macrophage apoE secretion and sterol efflux by the LDL receptor", J Lipid Res, 48, pp.366~372 (2007)
- Miyata M, "Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides", Nat Genet, 14, pp.55~61 (1996)
- Hu P, "Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations", Mol Biol Rep, 38, pp.489~494 (2011)