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http://purl.uniprot.org/citations/19747803http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19747803http://www.w3.org/2000/01/rdf-schema#comment"

Background and aims

A substantial number of subjects with autosomal dominant hypercholesterolemia (ADH) do not have LDL receptor (LDLR) or apolipoprotein B (APOB) mutations. Some ADH subjects appear to hyperabsorb sterols from the intestine, thus we hypothesized that they could have variants of the Niemann-Pick C1-Like 1 gene (NPC1L1). NPC1L1 encodes a crucial protein involved in intestinal sterol absorption.

Methods and results

Four NPC1L1 variants (-133A>G, -18C>A, 1679C>G, 28650A>G) were analyzed in 271 (155 women and 116 men) ADH bearers without mutations in LDLR or APOB aged 30-70years and 274 (180 women and 94 men) control subjects aged 25-65years. The AC haplotype determined by the -133A>G and -18C>A variants was underrepresented in ADH subjects compared to controls (p=0.01). In the ADH group, cholesterol absorption/synthesis markers were significantly lower in AC homozygotes that in all others haplotypes. Electrophoretic mobility shift assay (EMSA) results revealed that the -133A-specific oligonucleotide produced a retarded band stronger than the -133G allele. Luciferase activity with NPC1L1 -133G variant was 2.5-fold higher than with the -133A variant.

Conclusion

The -133A>G polymorphism exerts a significant effect on NPC1L1 promoter activity. NPC1L1 promoter variants might explain in part the hypercholesterolemic phenotype of some subjects with nonLDLR/nonAPOB ADH."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.org/dc/terms/identifier"doi:10.1016/j.numecd.2009.03.023"xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Martin B."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Civeira F."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Pocovi M."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Cofan M."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Ros E."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Solanas-Barca M."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Rodriguez-Rey J.C."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Garcia-Otin A.L."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/author"Pampin S."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/name"Nutr Metab Cardiovasc Dis"xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/pages"236-242"xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/title"An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia."xsd:string
http://purl.uniprot.org/citations/19747803http://purl.uniprot.org/core/volume"20"xsd:string
http://purl.uniprot.org/citations/19747803http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19747803
http://purl.uniprot.org/citations/19747803http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19747803
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http://purl.uniprot.org/uniprot/#_A0A0C4DFX6-mappedCitation-19747803http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19747803
http://purl.uniprot.org/uniprot/#_Q9UHC9-mappedCitation-19747803http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19747803
http://purl.uniprot.org/uniprot/Q9UHC9http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/19747803
http://purl.uniprot.org/uniprot/A0A0C4DFX6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/19747803
http://purl.uniprot.org/uniprot/A0A0C4DGG6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/19747803
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