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Pro12Ala Sequence Variant of the PPARG Gene Is Associated with Postprandial Hypertriglyceridemia in Non-E3/E3 Patients with the Metabolic Syndrome

¹ Servicio de Endocrinología y Nutrición. Hospital Clínico Virgen de la Victoria de Málaga, Málaga, Spain.
² Fundación IMABIS (Instituto Mediterráneo para el Avance de la Biotecnología y la Investigación Sanitaria), Málaga, Spain.
³ Servicio de Endocrinología y Nutrición. Hospital Regional Universitario Carlos Haya, Málaga, Spain.

^aAddress correspondence to this author at: c/o Manuel Vazquez Montalban no. 1., Rincón de la Victoria. Málaga, Spain 29720. Fax 34-952-286704; e-mail fernando.cardona.exts{at}juntadeandalucia.es.

Background: Postprandial hypertriglyceridemia, a component of the metabolic syndrome, has varied etiology and involves many genes related to triglyceride metabolism. Variations in these genes may affect postprandial hypertriglyceridemia in the context of the metabolic syndrome.

Methods: We orally administered 60 g of fat overload to 74 patients with the metabolic syndrome. We then measured baseline concentrations of cholesterol, triglycerides, HDL cholesterol, apolipoprotein AI, apolipoprotein B, uric acid, and uric acid excretion; we also performed homeostasis model assessments of insulin resistance and insulin sensitivity. At 3 h, we measured triglycerides, cholesterol, apolipoprotein AI, and apolipoprotein B. Patients were considered to have postprandial hypertriglyceridemia if the difference in plasma triglycerides between baseline and 3 h after the test was 1.71 mmol/L or more. We also measured anthropometrical variables and classified the patients according to their peroxisome proliferative activated receptor, gamma (PPARG) gene and apolipoprotein E (APOE) genotype.

Results: Postprandial hypertriglyceridemia occurred in 64.7% of patients with the Ala12 allele vs 19.9% of the Pro12Pro patients, (P = 0.00032; odds ratio, 7.6), and in 87.5% of the patients with both the Ala12 allele and the non-E3/E3 APOE genotype (odds ratio, 23.8). Logistic regression analysis showed that PPARG and APOE sequence variants were associated with the presence of postprandial hypertriglyceridemia.

Conclusion: The Pro12Ala PPARG sequence variant together with a non-E3/E3 APOE genotype is associated with a high risk for postprandial hypertriglyceridemia in patients with the metabolic syndrome, indicating a close association between these genes and the regulation of lipoproteinase clearance.

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				D. Gallardo, R. N. Pena, M. Amills, L. Varona, O. Ramirez, J. Reixach, I. Diaz, J. Tibau, J. Soler, J. M. Prat-Cuffi, et al. Mapping of quantitative trait loci for cholesterol, LDL, HDL, and triglyceride serum concentrations in pigs Physiol Genomics, November 12, 2008; 35(3): 199 - 209. [Abstract] [Full Text] [PDF]

				M. Macias-Gonzalez, F. Cardona, M. Queipo-Ortuno, R. Bernal, M. Martin, and F. J. Tinahones PPAR{gamma} mRNA Expression Is Reduced in Peripheral Blood Mononuclear Cells after Fat Overload in Patients with Metabolic Syndrome J. Nutr., May 1, 2008; 138(5): 903 - 907. [Abstract] [Full Text] [PDF]