Association of apo A-IV 360 (Gln --> His) polymorphism with plasma lipids and lipoproteins: the Framingham Offspring Study.
The effect of a common apolipoprotein (apo) A-IV polymorphism (substitution of histidine for glutamine at position 360) on plasma lipid, lipoprotein cholesterol and lipoprotein(a) (Lp(a)) levels, and on low-density lipoprotein (LDL) particle size was examined by genotyping in 2322 Caucasian men and women (mean age: 48.9+/-10.1 years) participating in the Framingham Offspring Study (FOS). The relative frequencies of the apo A-IV-Gln (apo A-IV-1) and the apo A-IV-His (apo A-IV-2) alleles were 0.932 and 0.068, respectively, and were in Hardy-Weinberg equilibrium. No effect of the apo A-IV-2 genotype was observed on plasma triglyceride, total and lipoprotein cholesterol, and LDL particle size in either men or women after adjustment for age and body mass index. To avoid a possible interaction between the apo E genotype and the apo A-IV genotype, subgroup analyses were undertaken in 1,414 male and female subjects with the apo E3/3 genotype. Among women in this group there was a significant effect of the apo A-IV-2 allele on triglyceride levels (p=0.046). This effect was no longer significant after adjustment for age and BMI (p=0.074). No significant allele effect on other lipoprotein levels, including Lp(a), was noted in apo E3/3 men or women. We have also conducted a meta-analysis of our own data and of other studies found in the literature, indicating a significant lowering effect of apo A-IV-2 on plasma triglycerides, but no effects on other parameters. In conclusion, the apo A-IV-2 allele is associated with a modest reduction in plasma triglyceride levels in the general population.
Cendoroglo
Maysa S
MS
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Lahoz
Carlos
C
Martinez
Tania L R
TL
Ordovas
Jose M
JM
Lamon-Fava
Stefania
S
Cupples
L Adrienne
LA
Wilson
Peter W
PW
Schaefer
Ernst J
EJ
D000328:Adult; D001054:Apolipoproteins A / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D005973:Glutamine / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D014280:Triglycerides; C022205:apolipoprotein A-IV; D005973:Glutamine; D006639:Histidine; D002784:Cholesterol