title: Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity.
abstract: Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3 +/- 8.4 kg/m2). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa[k]/ fa[k]) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85%, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 +/- 6.5 kg/m2) and 68 non-obese (BMI 21.6 +/- 2.2 kg/m2) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Matsuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Hosoda
authors.forename: J
authors.initials: J
authors.lastname: Matsuda
authors.forename: H
authors.initials: H
authors.lastname: Masuzaki
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: N
authors.initials: N
authors.lastname: Azuma
authors.forename: K
authors.initials: K
authors.lastname: Natsui
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimasa
authors.forename: S
authors.initials: S
authors.lastname: Nishi
authors.forename: D B
authors.initials: DB
authors.lastname: Thompson
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin