Sc.D. (Nutrition and Epidemiology), 2006, Harvard School of Public Health

M.S. (Biology), 1998, University of Costa Rica

Gene-diet interactions and heart disease

The major goal of my research in this field is to determine whether naturally occurring sequence variation in genes involved in lipid metabolism interact with dietary intake and other life-style factors to affect risk of coronary heart disease. These genes include APOC3, APOA5 and PPARG. Apolipoprotein CIII (apoCIII) and AV (apoAV) regulate triglyceride metabolism in opposite ways. Also, several studies have shown that naturally occurring sequence variation in both APOC3 and APOA5 genes affects plasma triglyceride concentrations. By using analysis of single nucleotide polymorphisms (SNPs) in the APOC3 and APOA5 genes, I found an APOC3 haplotype, defined by mutations in its promoter, was associated with a higher risk of nonfatal myocardial infarction (MI) in the Costa Rica population. This association was independent of genetic variation in the APOA5 gene, and it was not completely mediated by changes on triglyceride concentrations. The risk associated with the APOC3 variant haplotype was mostly observed in lean people, maybe due to overexpression of the APOC3 gene in obese people regardless of mutations in the promoter. The PPARG gene is a major regulator of energy homeostasis and lipid metabolism. The Pro12Ala polymorphism has been widely associated with risk of type 2 diabetes. Several lines of evidence have shown that the Ala12 allele confers protection against development of type 2 diabetes. However, its role in relation to the risk of CHD is still unclear. As result of my research in this polymorphism, it was found that the Ala12 variant does not affect risk of MI by itself but it is modifier of the protective effect of dietary intake of polyunsaturated fat. In particular, the presence of the Ala12 allele attenuated the beneficial effect of polyunsaturated fat consumption over the risk of MI.

Population admixture, dietary factors and risk of CHD

Cardiovascular heart disease (CHD), as well as presence of CHD risk factors, varies between different ethnic groups. However, because genetic ancestry is highly correlated with life-style and environmental factors, the basis for racial differences in aspects of physiology and metabolism is unclear. One approach to address the genetics of complex disease is through the study of genetic admixture. Using ancestry informative markers, it is possible to disentangle the effects of genetic ancestry and lifestyle, such as diet, on the risk of CHD.

Development of statistical methods for use in case-control studies

Because case-control studies are a major instrument in the attempt to identify disease susceptibility markers of complex diseases, I am working in the development of new statistical methods to use in population-based studies. One of the first results of this line of research has been the development of a method to estimate differential transmission of alleles in case-control studies. The next step would be the validation of this method using genotypes of case-parent trios.

Azofeifa J., Ruiz-Narvaez E., and Barrantes R. Genetic variation and racial admixture in the Miskito of the southern Mosquito Shore, Nicaragua. Rev. Biol. Trop. 1998, 46: 157-165

Solis M., Alvarado M., Ruiz-Narvaez E., Carrillo J., Navarrete M., Sanchez G., and Jimenez E. Cytogenetics and cytochemistry of leukemia patients in 2 neotropical hospitals. Rev. Biol. Trop. 2000, 48: 707-717

Azofeifa J., Ruiz-Narvaez E., and Barrantes R. Blood group, red cell, and serum protein variation in the Cabecar and Huetar, two Chibchan Amerindian tribes of Costa Rica. Am. J. Hum. Biol. 2001, 13: 57-64

Ruiz-Narvaez E., and Castro N. A simple method to estimate percentage parasitism when host and parasitoid phenologies are unknown. A statistical approach. Biocontrol 2003, 48: 87-100

Ruiz-Narvaez E and Campos H. Transmission disequilibrium test (TDT) for case-control studies. Eur. J. Hum. Genet. 2004, 12: 105-114

Yang Y, Ruiz-Narvaez E, Niu T, Xu X and Campos H. Genetic variants of the lipoprotein lipase gene and myocardial infarction in the Central Valley of Costa Rica. J. Lipid Res. 2004, 45: 2106-2109.

Azofeifa J, Hahn M, Ruiz-Narvaez E, Hummerich L, Morales A, Jimenez G and Barrantes R. The STR polymorphism (AAAAT) within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe. Rev. Biol. Trop. 2004, 52: 645-657.

Ruiz-Narvaez E, Santos F, Carvalho-Silva D, Azofeifa J, Barrantes R and Pena S. Genetic variation of the Y chromosome in Chibcha-speaking Amerindians of Costa Rica and Panama. Hum. Biol. 2005, 77: 71-91.

Ruiz-Narvaez E. Is the Ala12 variant of the PPARG gene an “unthrifty allele”? J. Med. Genet. 2005, 42: 547-550

Kabagambe E, Baylin A, Ruiz-Narvaez E, Siles X and Campos H. Decreased consumption of dried mature beans is positively associated with urbanization and nonfatal acute myocardial infarction. J. Nutr. 2005, 135: 1770-1775

Ruiz-Narvaez E, Yang Y, Nakanishi Y, Kirchdorfer J and Campos H. APOC3/A5 haplotypes, lipid levels and risk of myocardial infarction in the Central Valley of Costa Rica. J. Lipid Res. 2005, 46: 2605-2613

Kabagambe E, Baylin A, Ruiz-Narvaez E, Rimm EB and Campos H. Alcohol intake, drinking patterns, and risk of nonfatal acute myocardial infarction in Costa Rica. Am. J. Clin. Nutr. 2005, 82: 1336-1345

Gomez LM, Camargo JF, Castiblanco J, Ruiz-Narvaez E, Cadena J, Anaya JM. Analysis of IL1B, TAP1, TAP2 and IKBL polymorphisms on susceptibility to tuberculosis. Tissue Antigens 2006, 67: 290-296.

Baylin A, Ruiz-Narvaez E, Kraft P and Campos H. Alpha-linolenic acid, D6 desaturase gene polymorphism, and risk of nonfatal myocardial infarction. Am. J. Clin. Nutr. 2007, 85: 554-560.

Gomez LM, Ruiz-Narvaez E, Rojas–Villarraga A, Pineda-Tamayo R, Anaya JM. TNF Polymorphism as a Primary Risk Factor for Rheumatoid Arthritis. Confirming evidence in Northwestern Colombians. Clinical and Experimental Rheumatology 2007, 25: 443-448.

Gomez LM, Sanchez E, Ruiz-Narvaez E, Lopez-Nevot M, Anaya JM, Martin J. Macrophage migration inhibitory fator (MIF) gene influences the risk of developing tuberculosis in Northwestern Colombians. Tissue Antigens 2007, 70: 28-33.

Ruiz-Narvaez E, Kraft P, Campos H. The Ala12 variant of the PPARG gene is associated with higher polyunsaturated fat in adipose tissue and attenuates the protective effect of polyunsaturated fat intake on the risk of MI. Am. J. Clin. Nutr. 2007, 86: 1238-1242.

Ruiz-Narvaez E, Campos H. Evolutionary rate heterogeneity of Alu repeats upstream of the APOA5 gene: do they regulate APOA5 expression? J. Hum. Genet. 2008 (Epub ahead of print) DOI 10.1007/s10038-008-0245-7.

Yang Y, Ruiz-Narvaez E, Kraft P, Campos H. Effect of apolipoprotein E genotype and saturated fat intake on plasma lipids and myocardial infarction in the Central Valley of Costa Rica. Hum. Biol. 2007 (in press).

Ruiz-Narvaez E, Sacks F, Campos H. Abdominal obesity and hyperglycemia mask the effect of a common APOC3 haplotype on the risk of myocardial infarction. Am. J. Clin. Nutr. 2008 (in press).