Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0154251 (lipid disorder)
 795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial combined hyperlipidemia (FCHL) is a common genetic lipid disorder that is present in 10% of patients with premature coronary artery disease (CAD). It was the objective of the present study to evaluate the possible involvement of the PPARA locus in the pathophysiology of FCHL. Mutation detection analyses of the six coding PPARA exons resulted in the identification of four novel variants, [C/T] intron 3, S234G, [G/A] intron 5, and [C/A] 3(') UTR in three FCHL probands, whereas no novel variants were identified in spouses. In a case-control study, markers D22S275 and D22S928 were shown not to be associated with FCHL. However, D22S928, mapped within 1Mb of the PPARA gene, was shown to have a modifying effect on plasma apoCIII concentrations (P=0.011) and the combined hyperlipidemic FCHL phenotype (P=0.038). In addition two PPARA polymorphisms in intron 2 and 7 were studied, but these were not associated with FCHL. The frequency of the L162V variant was less in FCHL probands (1.98%) compared to that in spouses (4.84%). These results clearly demonstrate the genetically complex nature of FCHL and identify the PPARA gene as a modifier of the FCHL phenotype.
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PMID:Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia. 1246 72

Familial combined hyperlipidemia (FCH), characterized by multiple lipoprotein phenotypes, is the most common hereditary lipid disorder in humans. A mutant mouse strain, HcB-19, with similar biochemical features as FCH patients, has recently been identified. The mutation causing the FCH phenotype in these mice is located in the thioredoxin interacting protein (TXNIP) gene. The TXNIP gene in mice is located on chromosome 3F2.2, which is syntenic to chromosome 1q21 in humans, a region where several groups have positioned a locus for FCH. To evaluate the potential role of TXNIP in the FCH phenotype in humans, we analyzed the coding region, 5' UTR and introns of the TXNIP gene by direct sequencing in 10 well-defined patients with FCH and 5 healthy controls. We did not find any sequence variants in these regions of the TXNIP gene in patients with FCH. Our results suggest that different genes are involved in the FCH phenotype in humans compared to mice. We conclude that in our Dutch FCH patients, the TXNIP gene, based on its intronic, exonic, and 5' UTR sequences, is not involved as a major contributor to the FCH phenotype. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.
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PMID:Thioredoxin interacting protein in Dutch families with familial combined hyperlipidemia. 1536 98