Association and linkage between an insulin-like growth factor-1 gene polymorphism and fat free mass in the HERITAGE Family Study

G. Sun, J. Gagnon, Y. C. Chagnon, L. Pérusse, J. P. Després, A. S. Leon, J. H. Wilmore, J. S. Skinner, I. Borecki, D. C. Rao, C. Bouchard

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OBJECTIVE: To investigate the relationship between a DNA microsatellite marker in the insulin-like growth factor-1 (IGF-1) gene and body composition phenotypes before and following exposure to 20 weeks of aerobic exercise training in the HERITAGE Family Study. DESIGN: A controlled intervention study: fat mass (FM), percentage body fat (%FAT), fat free mass (FFM), body mass index (BMI) and abdominal visceral fat (AVF) at baseline (B) and in response to training (Δ = post minus pre-training value) were measured. Association and sib-pair linkage studies were undertaken. SUBJECTS: A maximum of 502 Caucasian individuals (99 families; 190 parents and 312 adult offspring). MEASUREMENTS: The polymorphism was typed by polymerase chain reaction and DNA sequencer. The body composition phenotypes were determined from the underwater weighing method, and AVF was assessed by computerized tomography scan. RESULTS: 11 alleles were found: the lengths ranged from 189 to 209 base pairs (bp), and the frequency of the most common allele, 189 bp, reached 0.71. In association studies, significant differences for B-FM, B-FFM and B-%FAT among the three genotypes (189bp homozygotes, heterozygotes and non-carriers) were detected. The B-FM for 189 bp homozygotes was 19.7 ± 0.6 kg, but 21.6 ± 0.7 and 21.3 ± 1.5 kg for the 189 bp heterozygotes and the non-189 bp carriers respectively (P = 0.03 after adjustment for age, sex and generation). Differences among the three genotypes were also observed for B-%FAT (25.9 ± 0.5 versus 27.4 ± 0.6 and 26.6 ± 1.2 kg; P < 0.05) and B-FFM (53.7 ± 0.4 versus 54.9 ± 0.5 kg and 54.4 ± 1.0 kg; P < 0.05). No significant difference for B-AVF was found among the three genotypes. Following 20 weeks of endurance exercise, the 189bp homozygotes gained only about half the amount of FFM compared with the other two IGF-1 genotypes (0.3 ± 0.1 vs 0.7 ± 0.1 and 0.5 ± 0.2 kg; P = 0.005). A strong linkage was observed between the IGF-1 marker and the changes in FFM (308 pairs of full sibs, P = 0.0002) but only a suggestive linkage with B-AVF (352 pairs of full sibs, P < 0.02). CONCLUSION: Associations were detected between the IGF-1 gene marker and FM, %FAT and FFM at baseline, and a strong association with the changes in FFM in response to training. Moreover, the IGF-1 gene marker was found to be strongly linked to the changes in FFM in response to 20 weeks of endurance exercise and weakly linked to abdominal visceral fat in the sedentary state.

Original languageEnglish (US)
Pages (from-to)929-935
Number of pages7
JournalInternational Journal of Obesity
Issue number9
StatePublished - 1999

Bibliographical note

Funding Information:
We would like to thank Ms Monique Chagnon for her technical assistance. Thanks are also expressed to Francois Michaud for computer and software assistance. The HERITAGE Family Study is supported by the National Heart, Lung and Blood Institute through the following grants: HL47323 (A.S. Leon, PI); HL47317 (D.C. Rao, PI); HL147327 (J.S. Skinner, PI); HL47321 (J.H. Wilmore, PI); and HL47670 (C. Bouchard, PI). The present study is also partly supported by The Life Fitness Academy of the U.S.A. through a grant for junior investigator (Guang Sun). Some of the results of this study were obtained with the program SAGE whose development was supported by the U.S. Public Health Service Research Grant 1P41RR03655) from the National Center for Research Resources. Further, Art Leon is partially supported by the Henry L. Taylor Professorship in Exercise Science and Health Enhancement and Claude Bouchard is supported by the Donald B. Brown Research Chair on Obesity funded by the Medical Research Council of Canada and Hoffmann La Roche Canada.


  • Abdominal visceral fat
  • Allelic variation
  • Endurance training
  • Family study
  • Fat free mass
  • Fat mass


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