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

Int J Obes Relat Metab Disord. 1999 Sep;23(9):929-35. doi: 10.1038/sj.ijo.0801021.


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 (delta=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 (189 bp 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 189 bp 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Arizona
  • Body Composition / genetics*
  • DNA / analysis
  • DNA Primers
  • Dinucleotide Repeats / genetics
  • Exercise*
  • Family*
  • Female
  • Humans
  • Indiana
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Middle Aged
  • Minnesota
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Texas
  • White People / genetics*


  • DNA Primers
  • Insulin-Like Growth Factor I
  • DNA