Originals

Diabetologia

, Volume 40, Issue 10, pp 1204-1210

Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity

  • N. MatsuokaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , Y. OgawaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , K. HosodaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , J. MatsudaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , H. MasuzakiAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , T. MiyawakiAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , N. AzumaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , K. NatsuiAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • , H. NishimuraAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
    • , Y. YoshimasaAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
    • , S. NishiAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
    • , D. B. ThompsonAffiliated withClinical Diabetes and Nutrition Section, National Institute Diabetes and Digestive and Kidney Diseases, National Institute of Health, Phoenix, Arizona, USA
    • , K. NakaoAffiliated withDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan

Summary

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. [Diabetologia (1997) 40: 1204–1210]

Keywords Leptin leptin receptor Ob-R obesity sequence variant.