Frequencies of apolipoprotein A4 gene polymorphisms and association with serum lipid concentrations in two healthy Spanish populations.
Apolipoprotein A4 (apoA4) 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 apoA4 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 2 Spanish regions differing in latitude and fat intake: Aragón and Comunidad Valenciana. Subjects were matched one to one by sex and age. Frequencies for the less common alleles were similar in both regions: 0.096 (95% CI: 0.111-0.081) for codon 360 and 0.196 (95% CI: 0.216-0.176) for codon 347. In men and women there was no association between the codon 360 polymorphism and total cholesterol or triglyceride levels. However, subjects carrying the 360His allele had low-density lipoprotein (LDL) cholesterol concentrations statistically lower than homozygotes for the 360Gln allele, even after further adjustment for sex, age, region, body mass index, and APOE polymorphism (p = 0.043). The less common allele at codon 347 (the 347Ser allele) was associated with increased LDL-cholesterol concentrations with a clear gene-dosage effect after multivariate adjustment (p = 0.029). Although these polymorphisms showed no heterogeneity by geographic region, the magnitude of the effect was higher in subjects from Aragón 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-cholesterol concentrations, supporting the antagonistic effect between the 360His and the 347Ser alleles on this trait.
Gañán
A
A
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
Corella
D
D
Guillén
M
M
Ordovás
J M
JM
Pocoví
M
M
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D001054:Apolipoproteins A / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D011110:Polymorphism, Genetic; D013030:Spain
D001054:Apolipoproteins A; D008055:Lipids