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United States Department of Agriculture

Agricultural Research Service


Location: Boston, Massachusetts

2012 Annual Report

1a. Objectives (from AD-416):
1. Identify new human genes involved in the homeostasis of lipid metabolism using genome-wide association studies and bioinformatics. 2. Identify candidate genes for overweight and obesity in humans with special emphasis on those modulating the risk for the metabolic syndrome. 3. Identify genetic factors determining differential susceptibility towards chronic disorders in response to a Western-type diet and lifestyle in humans with differing ethnic backgrounds. 4. Identify new longevity genes and describe their modulation by nutritional and environmental factors in animals and humans.

1b. Approach (from AD-416):
Because the predisposition to most common ailments affecting healthy aging and the responses of the individual to nutrients both contain a strong genetic component, our approach aims to uncover sets of genes involved in the predisposition to alterations in fasting and non fasting lipid metabolism and obesity and dietary response and to describe specific gene-diet interactions. This will be tested, using high throughput genotyping techniques, both in ongoing studies of free-living populations from different ethnic groups and in the metabolic ward (intervention studies). Our primary focus is to describe gene-diet interactions affecting/influencing progression of the metabolic syndrome, in particular obesity and dyslipidemia, often precursors to cardiovascular disease and diabetes. Cardiovascular candidate genes, both those previously described in the literature as well as those we identify through new genetic technologies and bioinformatics analysis will be used to examine associations and interactions on various scales. These include genetic variations, disease-related phenotypes and specific nutrients [fatty acids, cholesterol, fiber) and behavioral habits (alcohol consumption, smoking, physical (in-activity]. Rigorous statistical analysis will uncover the associations between phenotypes indicative of increased risk of metabolic syndrome and the genes responsible for such. Because cardiovascular disease and diabetes are traditionally considered diseases of the aged, we will also continue with our investigations to identify genes responsible for healthy aging. The principal approach taken for these studies involves gene expression microarray in silico analysis of animal models of aging and longevity. Candidate aging genes will then be studied in human populations.

3. Progress Report:
This progress report includes the work of one subordinate project at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-077-01S (Nutrition, cardiovascular health and Genomics).

4. Accomplishments

Review Publications
Parnell, L.D., Lee, Y., Lai, C. 2010. Adaptive genetic variation and heart disease risk. Current Opinion in Lipidology. 21(2):116-122.

Parnell, L.D., Lindenbaum, P., Shameer, K., Dall'Olio, G.M., Swan, D.C., Jensen, L.J., Cockell, S.J., Pedersen, B.P., Mangan, M.E., Miller, C., Albert, I. 2011. BioStar: an online question & answer resource for the bioinformatics community. PLoS Computational Biology. 7:e1002216.

Parnell, L.D. 2012. Advances in technologies and study design. In: Bouchard, C., Ordovas, J.M., editors. Progress in Molecular Biology and Translational Science. New York, NY: Elsevier Inc. 108:17-50.

Casasnovas, J.A., Alcalde, V., Civeira, F., Guallar, E., Ibanez, B., Jimenez-Borreguero, J., Laclaustra, M., Leon, M., Ordovas, J.M., Pocovi, M., Sanz, G., Fuster, V. 2012. Aragon workers' health study - design and cohort description. BioMed Central - Cardiovascular Disorders. 12(1):45.

Gomez-Abellan, P., Madrid, J., Ordovas, J.M., Garaulet, M. 2012. Chronobiological aspects of obesity and metabolic syndrome. Endocrinology and Nutrition. 59(1):50-61.

Ye, X., Lai, C., Crott, J., Troen, A., Ordovas, J., Tucker, K. 2011. The folate hydrolase 1561 C>T polymorphism is associated with depressive symptoms in Puerto Rican adults. Psychosomatic Medicine. 73(5):385-392.

Smith, C.E., Arnett, D.K., Corella, D., Tsai, M.Y., Lai, C., Parnell, L.D., Lee, Y., Ordovas, J.M. 2012. Perilipin polymorphism interacts with saturated fat and carbohydrates to modulate insulin resistance. Nutrition, Metabolism and Cardiovascular Diseases. 22(5):449-455.

Gesteiro, E., Bastida, S., Vazquez-Valasco, M., Corella, D., Guillen, M., Ordovas, J.M., Sanchez-Muniz, F.J. 2011. Effects of APOA5 S19W polymorphism on growth, insulin sensitivity and lipoproteins in normoweight neonates. European Journal of Pediatrics. 170(12):1551-1558.

Peter, I., Huggins, G.S., Ordovas, J.M., Haan, M., Seddon, J.M. 2011. Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study. Journal of Ophthalmology. 152(6):1005-1013.

Gomez-Abellan, P., Madrid, J.A., Lujan, J.A., Frutos, M.D., Gonzalez, R., Martinez-Augustin, O., Sanchez De Medina, F., Ordovas, J.M., Gauralet, M. 2012. Sexual dimorphism in clock genes expression in human adipose tissue. Obesity Surgery. 22(1):105-112.

Gomez-Abellan, P., Gomez-Santos, C., Madrid, J.A., Milagro, F.I., Campion, J., Martinez, J.A., Lujan, J.A., Ordovas, J.M., Garaulet, M. 2011. Site-specific circadian expression of leptin and its receptor in human adipose tissue. Nutricion Hospitalaria. 26(6):1394-1401.

Frazier-Wood, A.C., Ordovas, J.M., Straka, R.J., Hixson, J.E., Borecki, I.B., Tiwari, H.K., Arnett, D.K. 2012. The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: the GOLDN study. The Pharmacogenomics Journal. DOI: 10.1038/TPJ.2012.9.

Tsai, A.K., Steffen, B.T., Ordovas, J.M., Straka, R.J., Zhou, X., Hanson, N.Q., Arnett, D.K., Tsai, M.Y. 2011. Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants. Translational Research. 58(2):99-105.

Cowley, A.W., Nadeau, J.H., Baccarelli, A., Berecek, K., Fornage, M., Gibbons, G.H., Harrison, D.G., Liang, M., Nathanielsz, P.W., O'Connor, D.T., Ordovas, J.M., Peng, W., Soares, M., Szyf, M., Tolunay, H.E., Wood, K.C., Zhao, K., Galis, Z.S. 2012. Report of the National Heart, Lung, and Blood Institute Working Group on epigenetics and hypertension. Hypertension. 59(5):899-905.

Ordovas, J., Robertson, R., Cleirigh, E. 2011. Gene-gene and gene-environment interactions defining lipid-related traits. Current Opinion in Lipidology. 22(2):129-136.

Mata, N., Alonso, R., Badimon, L., Padro, T., Fuentes, F., Muniz, O., Perez-Jimenez, F., Lopez-Miranda, J., Diaz, J.L., Vidal, J.I., Barba, A., Piedecausa, M., Sanchez, J.F., Irigoyen, L., Guallar, E., Ordovas, J.M., Mata, P. 2011. Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART). Lipids in Health and Disease. DOI: 10.1186/1476-511X-10-94.

Mattei, J., Demissie, S., Tucker, K.L., Ordovas, J.M. 2011. The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study. Nutrition Metabolism and Cardiovascular Disease. 21(11):862-870.

Garaulet, M., Ordovas, J.M., Gomez-Abellan, P., Martinez, J.A., Madrid, J.A. 2011. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism. Journal of Cellular Physiology. 226(8):2075-2080.

Zachariah, J.P., Pencina, M.J., Lyass, A., Kaur, G., D'Agostino, R.B., Ordovas, J.M., Vasan, R.S. 2011. Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community. Journal of Hypertension. 29(5):863-868.

Aslibekyan, S., Jensen, M.K., Campos, H., Linkletter, C.D., Loucks, E.B., Ordovas, J.M., Deka, R., Rimm, E.B., Baylin, A. 2012. Fatty acid desaturase gene variants, cardiovascular risk factors, and myocardial infarction in the costa rica study. Frontiers in Genetics. 3:72.

Aslibekyan, S., Jensen, M.K., Campos, H., Linkletter, C.D., Loucks, E.B., Ordovas, J.M., Deka, R., Rimm, E.B., Baylin, A. 2012. Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction. European Journal of Clinical Nutrition. 66(3):353-359.

Frazier-Wood, A.C., Glasser, S., Garvey, W.T., Kabagambe, E.K., Borecki, I.B., Tiwari, H.K., Tsai, M.Y., Hopkins, P.N., Ordovas, J.M., Arnett, D.K. 2011. A clustering analysis of lipoprotein diameters in the metabolic syndrome. Lipids in Health and Disease. 10:237.

Wojczynski, M.K., Glasser, S.P., Oberman, A., Kabagambe, E.K., Hopkins, P.N., Tsai, M.Y., Straka, R.J., Ordovas, J.M., Arnett, D.K. 2011. High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN): an interventional study. Lipids in Health and Disease. 10:181.

Hernandez-Morante, J.J., Gomez-Santos, C., Margareto, J., Formiguera, X., Martinez-Carlos, M., Gonzalez, R., Martinez-Augustin, O., Madrid, J.A., Ordovas, J.M., Garaulet, M. 2011. Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women. Age. DOI 10.1007/s11357-011-9309-2.

Frazier-Wood, A.C., Glasser, S.P., Garvey, W.T., Kabagambe, E.K., Borecki, I.B., Tiwari, H.K., Tsai, M.Y., Hopkins, P.N., Ordovas, J.M., Arnett, D.K. 2011. Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS. Lipids in Health and Disease. 10:143.

Frazier-Wood, A.C., Kabagambe, E.K., Borecki, I.B., Tiwari, H.K., Ordovas, J.M., Arnett, D.K. 2012. Preliminary evidence for an association between LRP-1 genotype and body mass index in humans. PLoS One. 7(2):e30732.

Bouchard, C., Ordovas, J.M. 2012. Fundamentals of nutrigenetics and nutrigenomics. Progress in Molecular Biology and Translational Science. 108:1-15.

Aslibekyan, S., Campos, H., Loucks, E.B., Linkletter, C.D., Ordovas, J.M., Baylin, A. 2011. Development of a cardiovascular risk score for use in low- and middle-income countries. Journal of Nutrition. 141(7):1375-1380.

Van Rompay, M., Castaneda-Sceppa, C., Mckeown, N., Ordovas, J., Tucker, K. 2011. Prevalence of cardiovascular disease risk factors among older Puerto Rican adults living in Massachusetts. Journal of Immigrant and Minority Health. 13(5):825-833.

Garaulet, M., Esteban Tardido, A., Lee, Y., Smith, C., Parnell, L.D., Ordovas, J. 2012. SIRT1 and CLOCK 3111T greater than C combined genotype is associated with evening preference and weight loss resistance in a behavioral therapy treatment for obesity. International Journal of Obesity. DOI: 10.1038/ijo.2011.270.

Sanchez-Muniz, F., Schaefer, E.J., Ordovas, J. 2008. Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype. Journal of Nutrition. 139:13-19.

Laclaustra, M., Navas-Acien, A., Stranges, S., Ordovas, J., Guallar, E. 2009. Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004. Environmental Health Perspectives. 117(9):1409-1413.

Lai, C. 2012. Adaptive genetic variation and population differences. In: Bouchard, C., Ordovas, J. M., editors. Recent Advances in Nutrigenetics and Nutrigenomics. Oxford, UK: Elsevier. 108:461-489. PMID.22656388.

Shen, J., Lai, C., Mattei, J., Ordovas, J.M., Tucker, K.L. 2010. Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. American Journal of Clinical Nutrition. 91(2):337-342.

Kwak, J., Paik, J., Kim, O., Jang, Y., Lee, S., Ordovas, J., Lee, J. 2011. FADS gene polymorphisms in Koreans: association with _6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. Atherosclerosis. 214(1):94-100.

Junyent, M., Tucker, K., Shen, J., Lee, Y., Smith, C., Mattei, J., Lai, C., Parnell, L.D., Ordovas, J. 2010. A composite scoring of genotypes discriminates coronary heart disesase risk beyond conventional risk factors in the Boston Puerto Rican Health Study. Nutrition Metabolism and Cardiovascular Disease. 20(3):157-164.

Perez-Martinez, P., Ordovas, J.M., Garcia-Rios, A., Delgado-Lista, J., Delgado-Casado, N., Cruz-Teno, C., Camargo, A., Yubero-Serrano, E., Rodriguez, F., Perez-Jimenez, F., Lopez-Miranda, J. 2011. Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state. Nutrition Metabolism and Cardiovascular Disease. 21(1):39-45.

Feitosa, M., An, P., Ordovas, J., Ketkar, S., Hopkins, P., Straka, R., Arnett, D., Borecki, I. 2011. Association of gene variants with lipid levels in response to fenofibrate is influenced by metabolic syndrome status. Atherosclerosis. 215(2):435-439.

Richardson, K., Lai, C., Parnell, L.D., Lee, Y., Ordovas, J. 2011. A genome-wide survey for SNPs altering microRNA seed sites identifies functional candidates in GWAS. Biomed Central (BMC) Genomics. 2:504.

Richardson, K., Louie-Gao, Q., Arnett, D., Parnell, L.D., Lai, C., Davalos, A., Fox, C., Demissie, S., Cupples, L., Fernandez-Hernando, C., Ordovas, J. 2011. The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site. PLoS One. 6(4):e17944.

Corella, D., Ordovas, J. 2012. Interactions between dietary n-3 fatty acids and genetic variants and risk of disease. British Journal of Nutrition. 107:S271-S283.

Ordovas-Montanes, J., Ordovas, J. 2012. Cholesterol, inflammasomes, and atherogenesis. Current Cardiovascular Risk Reports. 6(1):45-52.

Smith, C.E., Ordovas, J.M., Sanchez-Moreno, C., Lee, Y., Garaulet, M. 2012. Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity. International Journal of Obesity. 36(1):130-136.

Corbalan-Tutau, M., Madrid, J., Ordovas, J., Smith, C., Nicolas, F., Garaulet, M. 2011. Differences in daily rhythms of wrist temperature between obese and normal-weight women: associations with metabolic syndrome features. Society for Chronobiology International Conference Proceedings. 28(5):425-433.

Feng, R., Wu, Y., Jang, G., Ordovas, J.M., Arnett, D.K. 2011. A powerful test of parent-of-origin effects for quantitative traits using haplotypes. PLoS One. 6(12):e28909.

Lluis-Ganella, C., Subirana, I., Lucas, G., Tomas, M., Munoz, D., Senti, M., Salas, E., Sala, J., Ramos, R., Ordovas, J.M., Marrugat, J., Elosua, R. 2012. Assessment of the value of a genetic risk score in improving the estimation of coronary risk. Atherosclerosis. 222(2):456-463.

Garcia-Rios, A., Perez-Martinez, P., Mata, P., Fuentes, F., Lopez-Miranda, J., Alonso, R., Caballero, J., Mata, N., Perez-Jimenez, F., Ordovas, J.M. 2010. Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study. Nutrition Metabolism and Cardiovascular Disease. 21(12):957-963.

Shen, J., Arnett, D., Parnell, L.D., Lai, C., Straka, R., Hopkins, P., An, P., Feitosa, M., Ordovas, J. 2012. The effect of CYP7A1 polymorphisms on lipid responses to fenofibrate. Journal of Cardiovascular Pharmacology. 59(3):254-259.

Cusano, N., Kiel, D., Demissie, S., Karasik, D., Cupples, L., Corella, D., Gao, Q., Richardson, K., Yiannakouris, N., Ordovas, J. 2012. A polymorphism in a gene encoding Perilipin 4 is associated with height but not with bone measures in individuals from the Framingham Osteoporosis Study. Calcified Tissue International. 90(2):96-197.

Perez-Martinez, P., Delgado-Lista, J., Garcia-Rios, A., Mcmonagle, J., Gulseth, H.L., Ordovas, J.M., Shaw, D.I., Karlstrom, B., Kiec-Wilk, B., Blaak, E.E., Helal, O., Malczewska-Malec, M., Defoort, C., Riserus, U., Saris, W., Lovegrove, J.A., Drevon, C.A., Roche, H.M., Lopez-Miranda, J. 2011. Glucokinase regulatory proten genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome. PLoS One. 6(6):e20555.

Last Modified: 10/16/2017
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