We previously reported the identification of a locus on mouse chromosome 6 that confers almost total resistance to atherogenesis, even on a hypercholesterolemic (LDL receptor-null) background. 5-Lipoxygenase (5-LO) is the rate-limiting enzyme in leukotriene synthesis and was among the chromosome 6 locus candidate genes that we examined. The levels of 5-LO mRNA were reduced about 5-fold in a con...

The low density lipoprotein receptor gene (LDLR) contains many Alu insertions, and is especially Alu-rich at its 3'-untranslated region (3'-UTR). Previous studies suggested that the LDLR 3'-UTR could regulate gene expression by the stabilization of its mRNA. Given the faster Alu evolutionary rate, and wondering about its consequences in a possibly regulatory locus, we have studied approximately...

Background: Familial hypercholesterolemia (FH) is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B 100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iran...

Low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogenic effects, but underlying molecular mechanisms remain poorly understood. Therefore, we studied effects of DMY on LDLR...

  Background and Objective: Familial hypercholesterolemia (FH) is an autosomal trait, which is caused by mutations in Low Density Lipoprotein Receptor (LDLR) gene. FH penetrance is about 100% and worldwide prevalence for heterozygous subjects is almost 1 in 500 and for homozygous 1 in 1,000,000. The patients are at risk of premature coronary heart disease (CHD) due to defective LDLR a...

Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the...

Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF/Ei x B6.129S7-Ldlr(tm1Her)) x C57BL/6J-Ldlr(tm1Her) backcross mice, homozygous for the Ldlr null allele, were fed a Western-type diet for 3 months and then killed for q...

BACKGROUND Genome-wide association studies for coronary artery disease/myocardial infarction revealed a 58 kb risk locus on 9p21.3. Refined genetic analyses revealed unique haplotype blocks conferring susceptibility to atherosclerosis per se versus risk for acute complications in the presence of underlying coronary artery disease. The cell proliferation inhibitor locus, CDKN2A, maps just upstre...

BACKGROUND Familial hypercholesterolemia (FH), a major risk for coronary heart disease, is predominantly associated with mutations in the genes encoding the low-density lipoprotein receptor (LDLR) and its ligand apolipoprotein B (APOB). RESULTS In this study, we characterize the spectrum of mutations causing FH in 2239 Czech probands suspected to have FH. In this set, we found 265 patients (1...