Common hepatic nuclear factor-4α variants are associated with high serum lipid levels and the metabolic syndrome

Daphna Weissglas-Volkov, Adriana Huertas-Vazquez, Elina Suviolahti, Jenny Lee, Christopher Plaisier, Samuel Canizales-Quinteros, Teresa Tusie-Luna, Carlos Aguilar-Salinas, Marja Riitta Taskinen, Päivi Pajukanta

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Hepatic nuclear factor-4α (HNF-4α), a transcription factor involved in the regulation of serum lipid and glucose levels, has recently been associated with type 2 diabetes. The HNF-4α 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.

Original languageEnglish (US)
Pages (from-to)1970-1977
Number of pages8
JournalDiabetes
Volume55
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

Keywords

  • AUC, area under the curve
  • Apo, apolipoprotein
  • CHD, coronary heart disease
  • FBAT, family-based association test
  • FCHL, familial combined hyperlipidemia
  • HBAT, haplotype-based association test
  • HNF-4α
  • Hepatic nuclear factor-4α

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Common hepatic nuclear factor-4α variants are associated with high serum lipid levels and the metabolic syndrome'. Together they form a unique fingerprint.

Cite this