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J Appl Physiol 95: 1425-1430, 2003. First published June 13, 2003; doi:10.1152/japplphysiol.00516.2003
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C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women

Stephen M. Roth,1,2 E. Jeffrey Metter,3 Mechele R. Lee,1 Ben F. Hurley,2 and Robert E. Ferrell1

1Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; 2Department of Kinesiology, University of Maryland, College Park, 20742; and 3Clinical Research Branch, National Institute on Aging, Gerontology Research Center, Baltimore, Maryland 21224

Submitted 14 May 2003 ; accepted in final form 11 June 2003

We performed gene screening of the ciliary neurotrophic factor receptor (CNTFR) gene and genotyped three newly identified polymorphisms: C-1703T in the 5' promoter region, T1069A in intron 5, and C174T in exon 9. We studied the association of these CNTFR variants with muscle strength, mass, and body composition in 465 men and women (20-90 yr) from the Baltimore Longitudinal Study of Aging. Only the C174T variant was significantly associated with muscle-related phenotypes. In the entire cohort, when corrected for age, sex, race, physical activity, and height, homozygotes for the common C allele at C174T (CC) exhibited lower total body mass and body mass index than carriers of the rare T allele, which appeared to be due to significant differences in total nonosseous fat-free mass (FFM) (48.0 ± 0.4 vs. 50.0 ± 0.7 kg; P = 0.011) and lower limb FFM (16.5 ± 0.1 vs. 17.2 ± 0.2 kg; P = 0.002). The CC group also exhibited significantly lower quadriceps concentric and eccentric isokinetic strength values at both 30 and 180°/s than the T allele carriers (all P < 0.04), but these differences were no longer significant after adjustment for lower limb FFM. There were no significant sex-by-genotype interactions. The results indicate that the C174T polymorphism in exon 9 of CNTFR is significantly associated with FFM in men and women, with concomitant differences in muscular strength.

genetics; muscle mass; muscle strength; polymorphism; sex; ciliary neurotrophic factor receptor


Address for reprint requests and other correspondence: S. M. Roth, Dept. Kinesiology, Univ. of Maryland, College Park, MD 20742 (E-mail: sroth1{at}umd.edu).




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