A large number of rare mutations in the low-density lipoprotein (LDL) receptor gene cause the autosomal dominant disorder familial hypercholesterolemia. In addition, a number of common DNA polymorphisms have been identified in the LDL receptor gene, but their significance in affecting plasma cholesterol levels in the general population has not been studied widely. We investigated the role of two common DNA polymorphisms, Ava II (exon 13) and Nco I (exon 18), at the LDL receptor locus in affecting plasma lipid profiles in normolipidemic Hispanics (n = 385) and non-Hispanic whites (NHWs; n = 543) from the San Luis Valley, Colorado. While the distribution of the Nco I polymorphism was comparable between Hispanics and NHWs, the allele frequencies at the Ava II restriction site differed significantly between the two ethnic groups (P < .001). The Ava II and Nco I polymorphisms were in linkage disequilibrium (P < .05) in both Hispanics and NHWs. Both polymorphisms revealed a gender-specific effect on total and LDL cholesterol (LDL-C) confined to women only in both ethnic groups. The AVA II polymorphism was associated significantly with total cholesterol and LDL-C in NHW women (P = .001 and P = .014) and in Hispanic women (P = .011 and P = .057). The effect of the Nco I polymorphism was significant on total cholesterol and LDL-C (P = .019 and P = .035) in Hispanic women only. Although a similar trend was observed in NHW women, the effect was not significant at the 5% level.(ABSTRACT TRUNCATED AT 250 WORDS)