Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women

Abstract

Objectives: To determine whether genetic variants in the ciliary neurotrophic factor (CNTF) gene are associated with muscle strength in older women.

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

Setting: Twelve contiguous ZIP code areas in Baltimore, Maryland.

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

Measurements: 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.

Conclusion: 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.