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1 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Kinesiology, University of Maryland, College Park, MD, USA
2 Gerontology Research Center, National Institutes of Health, Baltimore, MD, USA
3 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
4 Department of Kinesiology, University of Maryland, College Park, MD, USA
* To whom correspondence should be addressed. E-mail: sroth1{at}umd.edu.
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 BMI than carriers of the rare T allele (CT + TT), which appeared to be due to significant differences in total non-osseous 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 deg/sec 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.
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