Effects of apolipoprotein A-IV genotype on glucose and plasma lipoprotein levels

The effects of apolipoprotein (apo) A-IV genotype on serum glucose, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride and glucose concentrations were ascertained in a population of 373 men and 361 women with a mean age of about 57 years. Subjects were evaluated at entry into a lifestyle intervention program. Apolipoprotein A-IV genotype variations at residues 347 and 360 were examined, as these mutations affect the sequence of apo A-IV, a major protein constituent of intestinal triglyceride-rich lipoprotein and HDL. With regard to the apo A-IV 360 mutation, 16.4% of the females and 13.4% of the males carried the apo A-IV 2-allele, almost entirely in the heterozygous state. No effect of the apo A-IV 1/2 genotype was observed in either men or women on total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, the total cholesterol (TC)/HDL ratio, or on A-I, A-IV and apo B levels. This was also the case for the apo A-IV 347 mutation. However, women with the apo A-IV 360 1/2 genotype had significantly (p < 0.005) higher glucose levels (105.5 mg/dl) compared with the 1/1 wild-type (94.0 mg/dl). All analyses were also adjusted for age, body mass index, medications, alcohol use and cigarette smoking. The prevalence of the 347 mutation was somewhat higher than the 360 mutation, with 29% of the females and 32.0% of the males being heterozygous for this mutation, and 3.9% of the females and 5.4% of the males being homozygous for this mutation. These data are consistent with the concept that the apo A-IV 360 and 347 genotypes have no significant effect on apo A-IV levels and other lipid parameters in either gender. However, apo A-IV 360 1/2 genotype did have a significant effect on serum glucose levels in women.