In Caucasians, a histidine for glutamine substitution (Gln-->His) at residue 360 in apolipoprotein (apo) A-IV leads to an electrophoretically detectable polymorphism whose contribution to lipid metabolism regulation is controversial. In this study of 426 male and 188 female coronary heart disease patients, we analyzed the impact of this polymorphism on lipid metabolism, particularly high-density lipoprotein (HDL). The frequency of the rarer apo A-IV (360:His) allele was .069. This polymorphism exerted opposite effects in men and women in terms of serum concentrations of total cholesterol; triglycerides; HDL cholesterol; LDL cholesterol; lipoprotein (Lp) A-I; and apo A-I, A-II, and B. Only the difference in Lp A-I levels between male apo A-IV (360:Gln/Gln) homozygotes and apo A-IV (360:Gln/His) heterozygotes was significant (P < .05). In randomly selected subgroups of 38 male and 15 female apo A-IV (360:Gln/His) heterozygotes and 104 male and 15 female apo A-IV (360:Gln) homozygotes, heterozygosity for apo A-IV (360:Gln/His) in both sexes was associated with lower plasma cholesteryl ester transfer protein (CETP) activity (P < .05) and higher serum apo A-IV concentrations (P < .01 in men). Moreover, only men had significantly higher mean plasma activity levels of lecithin:cholesterol acyltransferase (LCAT) (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)