© 1997 American Heart Association, Inc.
Articles |
Codon 54 Polymorphism of the Human Intestinal Fatty Acid Binding Protein 2 Gene Is Associated With Dyslipidemias But Not With Insulin Resistance in Patients With Familial Combined Hyperlipidemia
From the Department of Medicine, University of Kuopio (Finland).
Correspondence to Markku Laakso, MD, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail markku.laakso{at}uku.fi
Abstract Familial combined hyperlipidemia (FCHL) is associated with variable expression of dyslipidemias and insulin resistance. In nondiabetic Pima Indians an A to G substitution in codon 54 of the fatty acid binding protein 2 (FABP2) gene has been shown to be associated with insulin resistance. We screened the entire coding region of this gene by single-strand conformation polymorphism analysis in 24 probands (17 men and 7 women; age, 63.0±7.4 years [mean±SD]; body mass index [BMI], 27.7±4.2 kg/m2) who had FCHL and in 40 healthy men from a random population sample of 82 men (age, 54.0±5.0 years; BMI, 26.3±3.2 kg/m2). Insulin resistance was assessed with the euglycemic clamp in 58 subjects from FCHL families (14 probands with FCHL and 44 first-degree relatives of probands: 38 men and 20 women; age, 51.5±12.6 years; BMI, 25.5±3.9 kg/m2). We found three nucleotide substitutions in the FABP2 gene: GCT to ACT (Ala
Thr) in codon 54, GTA to GTG in codon 118, and GCGCA to GCACA in the 3'-noncoding region. Frequencies of these variants did not differ between the patients and control subjects. The Ala to Thr substitution in codon 54 was associated with a high lipid oxidation rate (P=.011 after adjustment for sex and family relationship), high HDL triglycerides (P=.042), and high LDL triglycerides (P=.013) but not with insulin resistance in subjects from FCHL families. The FABP2 gene is unlikely to be a major gene for FCHL, but it might affect lipid metabolism in subjects with FCHL.
Key Words: fatty acid binding protein 2 • familial combined hyperlipidemia • insulin resistance
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