Influence of two apo A4 polymorphisms at codons 347 and 360 on non-fasting plasma lipoprotein-lipids and apolipoproteins in asian Indians

Apolipoprotein A-IV (apo A-IV, protein; apo A4, gene) is a major constituent of triglyceride-rich and high-density lipoprotein particles and may, therefore, play an important role in lipid metabolism. We studied the distribution of two apo A4 polymorphisms at codons 347 (alleles A and T) and 360 (alleles 1 and 2) in relation to plasma lipoprotein-lipid and apolipoprotein levels in 176 non-fasting male blood donors from New Delhi, Northern India. The frequencies of the T allele at codon 347 and the 2 allele at codon 360 were 0.12 and 0.03 respectively. Carriers of the T allele (AT and TT genotypes) had significantly lower plasma total cholesterol (P=0.04) and low density lipoprotein (LDL)-cholesterol (P=0.02) levels than individuals homozygous for the A allele (AA genotype). The codon 347 polymorphism explained 2.2 and 2.6% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The 2 allele at codon 360 was associated with marginally reduced plasma LDL-cholesterol (P=0.09) and increased triglyceride (P=0.05) levels compared to the 1 allele. To further elucidate the combined effects of the two polymorphism we constructed two-site haplotypes. The haplotype data showed a stronger influence and explained 3.0 and 5.2% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The two uncommon haplotypes, T1 and A2, were associated with 24.2 and 23.5 mg/dl lower total cholesterol and 22.5 and 42.0 mg/dl lower LDL-cholesterol levels, respectively. The accentuated effect of apo A4 polymorphisms on non-fasting plasma cholesterol suggest that apo A-IV may play an important role in regulating the postprandial metabolism of lipoproteins.