title: The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia.
abstract: OBJECTIVE
  Familial combined hyperlipidemia (FCH) is characterized by elevated levels of total cholesterol (TC), triglycerides (TG) and apolipoprotein B (apo B) and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin levels have also been associated with obesity, insulin resistance and atherosclerosis. Leptin exerts its effect through the leptin receptor (LEPR). The aim of this study is to determine whether the Gln223Arg polymorphism in the LEPR gene contributes to FCH and its associated phenotypes.
  
  
  METHODS
  The study population consists of 37 families, comprising 644 subjects, of whom 158 subjects were diagnosed as FCH. The FCH diagnosis was based on plasma TC and TG levels, adjusted for age and gender, and absolute apo B levels, according to our recently published nomogram. The Gln223Arg polymorphism was studied by restriction fragment length polymorphism-PCR.
  
  
  RESULTS
  Carriers of one or two Arg alleles had an increased risk of FCH, compared to subjects homozygous for the Gln allele (OR=1.6 [95% CI 1.0-2.4]). A difference in high-density lipoprotein cholesterol (HDL-c) levels was present between carriers and non-carriers of an Arg allele, 1.21 vs 1.28 mmol/l, respectively (P=0.04), but no differences in obesity, insulin resistance and other lipid parameters were found.
  
  
  CONCLUSIONS
  The Gln223Arg polymorphism in the LEPR gene is associated with FCH, which is supported by a significant association between HDL-c levels and the LEPR gene.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Nijmegen, The Netherlands. G.vandervleuten@aig.umcn.nl
authors.forename: G M
authors.initials: GM
authors.lastname: van der Vleuten
authors.forename: L A
authors.initials: LA
authors.lastname: Kluijtmans
authors.forename: A
authors.initials: A
authors.lastname: Hijmans
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: A F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: J
authors.initials: J
authors.lastname: de Graaf
mesh_terms: D000328:Adult; D000368:Aged; D000886:Anthropometry; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D014280:Triglycerides; D002784:Cholesterol