title: Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity.
abstract: The recently described putative lipostat system mediated in part by leptin and its hypothalamic receptor provides logical candidate genes for the molecular basis of inherited obesity in humans on the basis of the occurrence of profound obesity observed in obese and diabetic mice, in which the genes for leptin or its receptor, respectively, are mutated. In this study we tested the hypothesis that juvenile onset obesity in humans may be caused by leptin resistance mediated through genetic variations in isoforms of the hypothalamic leptin receptor. One hundred and fifty-six obese Danish men with a history of juvenile onset obesity were selected at the draft board examination with a body mass index (BMI) > or = 31 kg/m2. From the same study population a control group of 205 control subjects (mean BMI = 21,5 kg/m2) were randomly selected. Single strand conformational polymorphism scanning of genomic DNA from 56 obese subjects revealed a total of four amino acid variants located in coding exons 2, (Lys109Arg), 4 (Lys204Arg and Gln223Arg), and 12 (Lys656Asn), respectively. The codons 109, 223, and 656 variants were common, but their prevalence was not significantly different between obese and lean carriers with regard to allele or carrier frequency (p > 0.1 in each case). The codon 204 mutation was only found in one obese subject. In conclusion, it is unlikely that mutations in the coding region of the long isoform of the leptin receptor are a common cause of juvenile onset obesity.
authors.affiliation: Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
authors.forename: S M
authors.initials: SM
authors.lastname: Echwald
authors.forename: T D
authors.initials: TD
authors.lastname: Sørensen
authors.forename: T I
authors.initials: TI
authors.lastname: Sørensen
authors.forename: A
authors.initials: A
authors.lastname: Tybjaerg-Hansen
authors.forename: T
authors.initials: T
authors.lastname: Andersen
authors.forename: W K
authors.initials: WK
authors.lastname: Chung
authors.forename: R L
authors.initials: RL
authors.lastname: Leibel
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000596:Amino Acids / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000235:genetics*; D054411:Receptors, Leptin
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin