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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #170086
Title: FREQUENCIES OF APOLIPOPROTEIN A-IV GENE POLYMORPHISMS AND ASSOCIATION WITH SERUM LIPID CONCENTRATIONS IN TWO HEALTHY SPANISH POPULATIONS

Author
item GANON, A - UNIVERSITY OF ZARAGOZA
item CORELLA, D - UNIVERSITY OF VALENCIA
item GUILLEN, M - UNIVERSITY OF VALENCIA
item ORDOVAS, JOSE - TUFTS/HNRCA
item POCOVI, M - UNIVERSITY OF ZARAGOZA

Submitted to: Human Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/6/2003
Publication Date: 4/1/2004
Citation: Ganon, A., Corella, D., Guillen, M., Ordovas, J.M., Pocovi, M., 2004. Frequencies of apolipoprotein A-IV gene polymorphisms and association with serum lipid concentrations in two healthy Spanish populations. Human Biology. 76(2):253-266.

Interpretive Summary: Apolipoproteins are specific protein constituents of plasma lipoproteins which are well-recognized risk factors for heart disease. One of them, apolipoprotein (apo) A-IV, plays a role in intestinal dietary fatsorption. Several experimental interventions have shown that common variations at the APOA4 gene are associated with differences in plasma lipid response to dietary fat; however, association studies between these variants and plasma lipid concentrations in populations reveal mixed results. We examined the effects of these polymorphisms in 758 randomly selected subjects from two Spanish regions differing in latitude and fat intake: Aragón and Comunidad Valenciana. In men and women, there was no association between one of the polymorphisms known as the 360 codon polymorphism and total cholesterol or triglycerides. However, subjects carrying the form called 360His had LDL-C concentrations statistically lower than homozygotes for the so called 360Gln allele. The less common genetic form at the mutation known as codon 347 (347Ser allele) was associated with increased LDL-C concentrations. The magnitude of the effect was higher in subjects from Aragón as compared with the Comunidad Valenciana, suggesting a possible influence of the higher fat intake in Aragón. Therefore, as previously demonstrated in our previous work, the APOA4 gene is a candidate to investigate in terms of gene-diet interactions in the prevention of heart disease.

Technical Abstract: Apolipoprotein (apo) A-IV plays a role in intestinal lipid absorption. Several experimental interventions have shown that common variations at residues 347 (Thr>Ser) and 360 (Gln>His) on apoA-IV are associated with differences in plasma lipid response to dietary fat; however, association studies between these variants and plasma lipid concentrations in populations reveal mixed results. We examined the effects of these polymorphisms in 758 randomly selected subjects (mean age 36.7 +/- 9.5 years) from two Spanish regions differing in latitude and fat intake: Aragón and Comunidad Valenciana. Subjects were matched 1:1 by gender and age. Frequencies for the less common alleles were similar in both regions: 0.096 (95%CI: 0.111-0.081) for the codon 360, and 0.196 (95%CI: 0.216-0.176) for the 347. In men and women, there was no association between the 360 codon polymorphism and total cholesterol or triglycerides. However, subjects carrying the 360His had LDL-C concentrations statistically lower than homozygotes for the 360Gln allele, even after further adjustment for gender, age, region, body mass index and the apoE polymorphism (p=0.043). The less common allele at the codon 347 (347Ser allele) was associated with increased LDL-C concentrations with a clear gene-dosage effect after multivariate adjustment (p=0.029). Although there was not heterogeneity of these polymorphisms by geographical region, the magnitude of the effect was higher in subjects from Aragón as compared with the Comunidad Valenciana, suggesting a possible influence of the higher fat intake in Aragón. In the combined association analysis subjects with the 360Gln/347Ser pseudohaplotype had the highest LDL-C concentrations supporting the antagonistic effect between the 360His and the 347Ser alleles on this trait.