title: Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides.
abstract: Positive evidence has been reported for linkage and association between the upstream stimulatory factor 1 gene (USF1) and familial combined hyperlipidemia (FCHL). We genotyped the two most positive single-nucleotide polymorphisms (SNPs) (usf1s1: rs3737787 and usf1s2: rs2073658) from previous studies in a large family sample. This sample included 2,195 subjects in 87 Utah pedigrees ascertained for early death due to coronary heart disease (CHD), early strokes, or early onset hypertension. There were a total of 262 relative pairs in these families with FCHL. In the full family sample, FCHL was associated with usf1s1 (P = 0.02). Triglyceride and LDL cholesterol defined qualitatively or quantitatively were also associated with usf1s1 (P = 0.02-0.05). Results were strengthened for qualitative and quantitative triglyceride and LDL cholesterol when data from males only was analyzed, revealing associations for usf1s1 (P = 0.001-0.02), usf1s2 (P = 0.02-0.05) and the haplotype of these two SNPs (P = 0.01-0.04). The strongest results were in the subset of subjects from families ascertained for premature stroke or hypertension, rather than those ascertained for premature CHD. This study replicates the involvement of USF1 in FCHL and related lipid traits in a family sample not ascertained for FCHL.
authors.affiliation: Neurodevelopmental Genetics Project, Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA. hilary@bach.med.utah.edu
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
authors.forename: Yuanpei
authors.initials: Y
authors.lastname: Xin
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hasstedt
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
mesh_terms: D017668:Age of Onset; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000235:genetics / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics*; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics / Q000401:mortality; D014157:Transcription Factors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*; D051720:Upstream Stimulatory Factors
chemical_list: D008078:Cholesterol, LDL; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D014280:Triglycerides; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors