Abstract
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.
