title: 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.
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 substitution 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.
authors.affiliation: Department of Medicine, University of Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: J
authors.initials: J
authors.lastname: Rissanen
authors.forename: S
authors.initials: S
authors.lastname: Heikkinen
authors.forename: L
authors.initials: L
authors.lastname: Karjalainen
authors.forename: M
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D003062:Codon; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005387:Finland; D005787:Gene Frequency; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics*; D006949:Hyperlipidemias / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D007422:Intestines; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018996:Myelin P2 Protein / Q000235:genetics*; D009363:Neoplasm Proteins; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D003062:Codon; C493404:FABP2 protein, human; C107608:FABP7 protein, human; C493405:Fabp2 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D008055:Lipids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins