title: Common hepatic nuclear factor-4alpha variants are associated with high serum lipid levels and the metabolic syndrome.
abstract: Hepatic nuclear factor-4alpha (HNF-4alpha), a transcription factor involved in the regulation of serum lipid and glucose levels, has recently been associated with type 2 diabetes. The HNF-4alpha gene (HNF4A) resides on chromosome 20q12-q13.1, which, in addition to type 2 diabetes, has also previously been linked to high triglycerides in Finnish familial combined hyperlipidemia (FCHL) families. FCHL, characterized by elevated levels of serum total cholesterol, triglycerides, or both, is a common dyslipidemia observed in up to 20% of patients with premature coronary heart disease. Considering the clear phenotypic overlap between type 2 diabetes and FCHL, both predisposing to high serum triglycerides and glucose intolerance, we tested this gene for association in dyslipidemic families originating from two distinct populations, Finnish and Mexican, and comprising 1,447 subjects. Our data show that common HNF4A variants and haplotypes are associated with elevated serum lipid levels and the metabolic syndrome (P = 0.008-0.04), as well as with elevated glucose parameters (P = 0.008-0.03), using family-based association analysis. Importantly, both Finnish and Mexican families shared two common lipid-associated HNF4A haplotypes (P = 0.005 for total cholesterol and 0.006 for triglycerides). In conclusion, we show for the first time that common HNF4A variants are associated with high serum lipid levels and the metabolic syndrome.
authors.affiliation: UCLA, Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, 695 Charles E. Young Dr. South, Los Angeles, CA 90095-7088, USA.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas-Vazquez
authors.forename: Elina
authors.initials: E
authors.lastname: Suviolahti
authors.forename: Jenny
authors.initials: J
authors.lastname: Lee
authors.forename: Christopher
authors.initials: C
authors.lastname: Plaisier
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.forename: Teresa
authors.initials: T
authors.lastname: Tusie-Luna
authors.forename: Carlos
authors.initials: C
authors.lastname: Aguilar-Salinas
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
mesh_terms: D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005387:Finland; D005787:Gene Frequency; D014644:Genetic Variation; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000235:genetics; D024821:Metabolic Syndrome / Q000235:genetics*; D008800:Mexico; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D014280:Triglycerides; D002784:Cholesterol