title: TXNIP gene not associated with familial combined hyperlipidemia in the NHLBI Family Heart Study.
abstract: Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, and is implicated in up to 20% of cases of premature coronary heart disease. Positive linkage to chromosome 1q was found in FCHL families participating in the NHLBI Family Heart Study (FHS), replicating linkage found in other studies. The HcB-19 mouse, which shares phenotypes with FCHL, was shown in other studies to have a nonsense mutation in the thioredoxin interacting protein gene (txnip). txnip is a gene on mouse chromosome 3 in a region syntenic with the 1q human FCHL linkage region. We re-sequenced the human homolog of mouse txnip in the FHS sample and identified nine single nucleotide polymorphisms (SNPs). We did not observe the nonsense mutation found in the HcB-19 mouse, and only three of the SNPs discovered were sufficiently polymorphic for analysis. No association between FCHL and the TXNIP gene was found. Within FCHL cases, presence of variants also did not significantly affect body mass index or levels of lipids, insulin, or glucose. Our results suggest that in this sample, TXNIP does not play a major role in FCHL or related traits, and is unlikely to account for the positive evidence of linkage in this region.
authors.affiliation: Neurodevelopmental Genetics Project, University of Utah, 421 Wakara Way, Suite 143, Salt Lake City, UT 84108, USA. hilary@wilbur.med.utah.edu
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
authors.forename: Nanda
authors.initials: N
authors.lastname: Singh
authors.forename: Diane
authors.initials: D
authors.lastname: Dunn
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Robert
authors.initials: R
authors.lastname: Weiss
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Mark F
authors.initials: MF
authors.lastname: Leppert
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011336:Probability; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013879:Thioredoxins / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human; D013879:Thioredoxins