Genetic factors associated with response of LDL subfractions to change in the nature of dietary fat

A preponderance of dense low density lipoprotein (LDL) particles is associa ted with an increased risk of coronary heart disease. It has been shown tha t dense LDL levels can be modified by diet. We investigated the contributio n of polymorphisms in the genes for apolipoprotein (apo) B, apo AIV, lipopr otein lipase (LPL) and cholesterol ester transfer protein (CETP) to variati on in the changes in plasma concentrations of dense LDL between a high satu rated and a high polyunsaturated fatty acid diet. A total of 46 freeliving individuals (19 men and 27 women) completed a crossover trial with two diet ary interventions of 4 weeks each, a high saturated fat diet (providing 21% energy from saturated fat and 3% energy from polyunsaturated fat) and a hi gh polyunsaturated fat diet (providing 11% energy as saturated fat and 10% energy as polyunsaturated fat). Overall, the change in dense LDL between th e saturated and polyunsaturated fat period was 0.17 +/- 0.33 mmol/L and thi s change was similar in men and women. Of the polymorphisms studied only va riation in the apo AIV gene causing the substitution of histidine for gluta mine at position 360 (Q360H) was associated with significant differences in the change in dense LDL concentration. Apo AIV Q/H individuals (n = 6) sho wed a three-fold greater change in dense LDL cholesterol unadjusted for Lp( a) levels than Q/Q individuals (0.46 +/- 0.27 versus 0.12 +/- 0.31 mmol/L, p = 0.02). The greater decrease in dense LDL cholesterol with an increase i n polyunsaturated fat seen in those with the apo AIV H360 variant, who repr esent roughly 10% of the general population, suggests that they may benefit most from a PUFA rich lipid lowering diet. (C) 2000 Elsevier Science Irela nd Ltd. All rights reserved.