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Title: Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study

Author
item GARCIA-RIOS, ANTONIO - Reina Sofia University
item PEREZ-MARTINEZ, PABLO - Cordoba University
item MATA, PEDRO - Iis-Fundacion Jimenez Diaz
item FUENTES, FRANCISCO - Reina Sofia University
item LOPEZ-MIRANDA, JOSE - Reina Sofia University
item ALONSO, RODRIGO - Iis-Fundacion Jimenez Diaz
item CABALLERO, JAVIER - Reina Sofia University
item MATA, NELVA - Madrid Health Authority And Fundacion
item PEREZ-JIMENEZ, FRANCISCO - Cordoba University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/2/2010
Publication Date: 12/1/2010
Citation: 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.

Interpretive Summary: High levels of blood low-density lipoprotein cholesterol, also known as bad cholesterol, have been associated with increased risk of cardiovascular disease. These concentrations are determined by a complex array of genetic and environmental factors, including diet. One of the genes more consistently associated with hypercholesterolemia (excess cholesterol) in the population at large is known as TRIB1. In addition to the genes associated with the common forms of hypercholesterolemia, other genes, such as the LDL receptor gene (LDLR) are responsible for a less common, but more harmful form known as familial hypercholesterolemia (FH). Therefore, our aims were to assess the association of one of the common variants of the TRIB1 gene, known as the rs17321515 single nucleotide polymorphism (SNP – variation in DNA sequencing) with plasma lipids concentrations and anthropometric variables and to explore the interaction between this SNP and some classic risk factors in patients with FH. For this purpose, the rs17321515 SNP was genotyped in 531 subjects with genetic diagnosis of FH. Subjects with the most common TRIB1 genotype A/A had significantly higher waist circumference compared with less common G allele subjects. Interestingly, we found that in smokers, the presence of the A/A genotype in the TRIB1 gene was associated with a lipid profile likely to accelerate hardening of the arteries. Therefore, variation and the TRIB gene in combination with smoking could explain the differences in the susceptibility to coronary heart disease in these patients.

Technical Abstract: rs17321515 SNP has been associated with variation in LDL-C, high density lipoprotein cholesterol and triglycerides concentrations. This effect has never been studied in patients with severe hypercholesterolemia. Therefore, our aims were to assess the association of the rs17321515 (TRIB1) SNP with plasma lipids concentrations and anthropometric variables and to explore the interaction between this SNP and some classic risk factors in patients with familial hypercholesterolemia (FH). rs17321515 SNP was genotyped in 531 subjects with genetic diagnosis of FH. Homozygous A/A had significantly higher waist circumference compared with G/G subjects (P = 0.006) and carriers of the minor allele G (P = 0.039). Interestingly, smokers homozygous for the A allele displayed higher plasma triglycerides concentrations (P = 0.029), higher VLDL-C levels (P = 0.023) and higher TC/HDL-C ratio (P = 0.035) than carriers of the minor allele G. In addition, homozygous A/A with the presence of arcus cornealis displayed lower plasma ApoA-I levels (P = 0.024) and higher TC/HDL-C ratio (P = 0.046) than carriers of the minor allele G. Smoking status and presence of arcus cornealis modulate the effect of rs17321515 (TRIB1) polymorphism on plasma lipids levels in patients with FH. These results could explain the differences in the susceptibility to coronary heart disease in these patients.