Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women.
OBJECTIVE
To determine whether genetic variants in the ciliary neurotrophic factor (CNTF) gene are associated with muscle strength in older women.


METHODS
Cross-sectional analysis of baseline data from the Women's Health and Aging Studies I (1992) and II (1994), complementary population-based studies.


METHODS
Twelve contiguous ZIP code areas in Baltimore, Maryland.


METHODS
Three hundred sixty-three Caucasian, community-dwelling women aged 70 to 79.


METHODS
Participants were genotyped at the CNTF locus for eight single nucleotide polymorphisms (SNPs), including the null allele rs1800169. The dependent variables were grip strength and the frailty syndrome, identified as presence of three or more of five frailty indicators (weakness, slowness, weight loss, low physical activity, exhaustion). In addition to genotypes, independent variables of body mass index (BMI) and osteoarthritis of the hands were included.


RESULTS
Using multivariate linear regression, single SNP analysis identified five SNPs significantly associated with grip strength (P<.05), after adjusting for age, BMI, and osteoarthritis. Haplotype analysis was performed, and a single haplotype associated with grip strength was identified (P<.01). The rs1800169 null allele fully explained the association between this haplotype and grip strength under a recessive model, with individuals homozygous for the null allele exhibiting a 3.80-kg lower (95% confidence interval=1.01-6.58) grip strength. No association was seen between the CNTF null allele and frailty.


CONCLUSIONS
Individuals homozygous for the CNTF null allele had significantly lower grip strength but did not exhibit overt frailty. Larger prospective studies are needed to confirm this finding and extend it to additional populations.
Arking
Dan E
DE
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 733 N. Broadway, Baltimore, MD 21205, USA.
Fallin
Daniele M
DM
Fried
Linda P
LP
Li
Tao
T
Beamer
Brock A
BA
Xue
Qian Li
QL
Chakravarti
Aravinda
A
Walston
Jeremy
J
D000368:Aged; D015992:Body Mass Index; D020934:Ciliary Neurotrophic Factor / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D016330:Frail Elderly; D005838:Genotype; D018737:Hand Strength / Q000502:physiology*; D006801:Humans; D007866:Leg / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*
D020934:Ciliary Neurotrophic Factor