Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Quebec Family Study

International Journal of Obesity

Volumn 23, Issue 3, 1999, Pages 278-286

  Chagnon, Y C ^a,c   Chung, W K ^b   Perusse L ^a   Chagnon, M ^a   Leibel, R L ^b   Bouchard, C ^a  

^a Phys Activity Sciences Laboratory   (Canada)

^b Och Spine at New York Presbyterian Hospitals   (United States)

^c Division of Kinesiology   (Canada)

Author keywords

Association; Fat free mass; Human obesity; Leptin receptor gene; Linkage

Indexed keywords

HETERODUPLEX; LEPTIN RECEPTOR; MICROSATELLITE DNA;

ADULT; AGED; AMINO ACID SUBSTITUTION; ARTICLE; BODY COMPOSITION; BODY FAT; BODY HEIGHT; BODY MASS; CANADA; COVARIANCE; DNA SEQUENCE; FAMILY STUDY; FEMALE; GEL; GENE FREQUENCY; GENETIC LINKAGE; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; OBESITY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SKINFOLD; STATISTICS;

EID: 0033021670     PISSN: 03070565     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.ijo.0800809     Document Type: Article

References (47)

1. 1 Bouchard C. Genetics of obesity: Overview and research directions. In: Bouchard C (ed). The Genetics of Obesity. CRC Press: Boca Raton, 1994, 223-233.
2. 2 Friedman JM, Leibel RL, Bahary N. Molecular mapping of obesity genes. Mamm Genome 1991; 1: 130-144.
3. 3 Coleman DL. Diabetes-Obesity Syndromes in Mice. Diabetes 1992; 31: 1-6.
4. 4 Chagnon YC, Bouchard C. The genetics of obesity: advances from rodent studies. Trends Genet 1996; 12: 441-444.
5. 5 Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546-549.
6. 6 Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973; 9: 294-298.
7. 7 Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543-546.
8. 8 Harris RBS, Hervey E, Hervey GR, Tobin G. Body composition of lean and obese Zucker rats in parabiosis. Int J Obes 1987; 11: 275-283.
9. 9 Maffei M, Fei H, Lee GH, Dani C, Leroy P, Zhang Y, Proenca R, Negrel R, Ailhaud G, Friedman JM. Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci USA 1995; 92: 6967-6960.
10. 10 Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540-543.
11. 11 Truett GE, Jacob HJ, Miller J, Drouin G, Bahary N, Smoller JW, Lander ES, Leibel RL. Genetic map of rat Chromosome 5 including the fatty (fa) locus. Mamm Genome 1995; 6: 25-30.
12. 12 Chua SC Jr, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, Leibel RL. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 1996; 271: 994-996.
13. 13 Chua SC, White DW, Wu-Peng XS, Liu SM, Okada N, Kershaw EE, Chung WK, Power-Kehoe L, Chua M, Tartaglia LA, Leibel RL. Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 1996; 45: 1141-1143.
14. 14 Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Caskey CT, Hess JF. Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet 1996; 13: 18-19.
15. 15 Iida M, Murakami T, Ishida K, Mizuno A, Kuwajima M, Shima K. Phenotype-linked amino acid alteration in leptin receptor cDNA fipom Zucker Fatty (fa/fa) rat. Biochem Biophys Res Commun 1996; 222: 19-26.
16. 16 Wu-Peng SX, Chua SC Jr, Okada N, Liu SM, Nicolson M, Leibel RL. Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr). Evidence for deficient plasma-to-CSF transport of leptin in both the zucker and Koletsky obese rat. Diabetes 1997; 46: 513-518.
17. 17 Takaya K, Ogawa Y, Hiraoka J, Hosoda K, Yamori Y, Nakao K, Koletsky RJ. Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat. Nat Genet 1996; 14: 130-131.
18. 18 White DW, Wang Y, Chua SC, Morgenstern JP, Leibel RL, Baumann H, Tartaglia LA. Constitutive and impaired signaling of leptin receptors containing the Gln→»Pro extracellular domain fatty mutation. Proc Natl Acad Sci USA 1997; 94: 10657-10662.
19. 19 Chua SC Jr, Koutras IK, Han L, Liu S-M, Kay J, Young SJ, Chung WK, Leibel RL. Fine structure of the murine leptin receptor gene: Splice site suppression is required to form two alternatively spliced transcripts. Genomics 1997; 45: 264-270.
20. 20 Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379: 632-635.
21. 21 Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84: 491-495.
22. 22 Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Molarty A, Moore KJ, Smutho JS, Mays GG, Woolf EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263-1271.
23. 23 Chung WK, Power-Kehoe L, Chua M, Leibel RL. Mapping of the OB receptor (OBR) to 1 p in a region of non-conserved gene order from mouse and rat to human. Genome Res 1996; 6: 431-438.
24. 24 Norman RA, Leibel RL, Chung WK, Power-Kehoe L, Chua SC Jr, Knowler WC, Thompson DB, Bogardus C, Ravussin E. Absence of linkage of obesity and energy metabolism to markers flanking homologues of rodent obesity genes in Pima Indians. Diabetes 1996; 45: 1229-1232.
25. 25 Norman RA, Thompson DB, Foroud T, Garvey WT, Bennett PH, Bogardus C, Ravussin E and other members of the Prime Diabetes Gene Group. Genomewide search for genes influencing percent body fat in Pima Indians: Suggestive linkage at chromosome 11q21-q22. Am J Hum Genet 1997; 60: 166-173.
26. 26 Norman RA, Tataranni PA, Pratley R, Thompson DB, Hanson RL, Prochazka M, Baier L, Ehm MG, Sakul H, Foroud T, Garvey WT, Burns D, Knowler WC, Bennert PH, Bogardus C, Ravussin E. Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. Am J Hum Genet 1998; 62: 659-668.
27. 27 Francke S, Clément K, Dina C, Inoue H, Behn P, Vatin V, Basdevant A, Guy-Grand B, Permutt MA, Froguel P, Hager J. Genetic studies of the leptin receptor gene in morbidly obese French caucasian families. Hum Genet 1997; 100: 491-496.
28. 28 Chagnon YC, Pérusse L, Lamothe M, Chagnon M, Nadeau A, Dionne FT, Gagnon J, Chung WK, Leibel RL, Bouchard C. Suggestive linkages between markers on human 1p32-p22 and body fat and insulin levels in the Quebec Family Study. Obes Res 1997; 5: 115-121.
29. 29 Considine RV, Considine EL, Williams CJ, Hyde TM, Caro JF. The hypothalamus leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. Diabetes 1996; 19: 992-994.
30. 30 Chung WK, Power-Kehoe L, Chua M, Lee R, Leibel RL. Genomic structure of the human OB receptor and the identification of two novel intronic microsatellites. Genome Res 1996; 6: 1192-1199.
31. 31 Chung WK, Power-Kehoe L, Chua M, Chu F, Devoto M, Aronne L, Huma Z, Sothern M, Udall JN, Kahle B, Leibel RL. Exonic and intronic variation in the leptin receptor (OBR) of obese humans. Diabetes 1997; 46: 1509-1511.
32. 32 Thompson DB, Ravussin E, Bennett PH, Bogardus C. Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Hum Mol Genet 1997; 6: 675-679.
33. 33 Gotoda T, Manning BS, Goldstone AP, Imrie H, Evans AL, Strosberg AD, McKeigue PM, Scott J, Aitman TJ. Leptin receptor gene variation and obesity: lack of association in a white British male population. Hum Mol Genet 1997; 6: 869-876.
34. 34 Echwald SM, Sorensen TD, Sorensen TIA, Tybjaerg-Hansen A, Andersen T, Chung WK, Leibel RL, Pedersen O. Amino acid variants in the human leptin receptor: Lack of association to juvenile onset of obesity. Biochem Biophys Res Commun 1997; 233: 248-252.
35. 35 Matsuoka N, Ogawa Y, Hosoda K, Matsuda J, Masuzaki H, Miyawaki T, Azuma N, Natsui K, Nishimura H, Yoshimasa Y, Nishi S, Thompson DB, Nakao K. Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity. Diabetologia 1997; 40: 1204-1210.
36. 36 Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte J-M, Basdevant A, Bougnères P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392: 398-401.
37. 37 Silver K, Walston J, Chung WK, Yao F, Parikh VV, Andersen R, Cheskin LJ, Elahi D, Muller D, Leibel RL, Shuldiner AR. The Gln223Arg and Lys656Asn polymorphisms in the human leptin receptor do not associate with traits related to obesity. Diabetes 1997; 46: 1898-1900.
38. 38 Bouchard C. Genetic epidemiology, association and sib-pair linkage: Results from The Québec Family Study. In: Bray GA, Ryan DH (eds). Molecular and Genetic Aspects of Obesity. Louisiana State University Press: Baton Rouge, 1996, 470-481.
39. 39 Behnke AR, Wilmore JH. Evaluation and regulation of body build and composition. Prentice-Hall: Englewood Cliffs, 1974.
40. 40 Siri WE. The gross composition of the body. Adv Biol Med Phys 1976; 4: 239-280.
41. 41 Himes JH, Bouchard C. Validity of anthropometry in classifying youths as obese. Int J Obes 1989; 13: 183-193.
42. 42 SAGE Statistical Analysis for Genetic Epidemiology, release 3.0. Computer program package available from the Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland. 1997.
43. 43 Green DA. Linkage analysis of necessary disease loci versus susceptibility loci. Am J Hum Genet 1993; 52: 135-143.
44. 44 Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994; 265: 2037-2048.
45. 45 Baumann H, Morella KK, White DW, Dembski M, Bailon PS, Kim H, Lai CF, Tartaglia LA. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Nat Acad Sci USA 1996; 93: 8374-8378.
46. 46 Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC. Defective STAT signalling by the leptin receptor in diabetic mice. Proc Nat Acad Sci USA 1996; 93: 6231-6235.
47. 47 Vaisse C, Halaas JL, Horvath CM, Darnell JJ, Stoffel M, Friedman JM. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 1996; 14: 95-97.