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. 2012;7(1):e29883.
doi: 10.1371/journal.pone.0029883. Epub 2012 Jan 10.

A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: the HALCyon programme

Tamuno Alfred  1 , Yoav Ben-Shlomo, Rachel Cooper, Rebecca Hardy, Cyrus Cooper, Ian J Deary, Tom R Gaunt, David Gunnell, Sarah E Harris, Meena Kumari, Richard M Martin, Avan Aihie Sayer, John M Starr, Diana Kuh, Ian N M Day; HALCyon study team
Collaborators, Affiliations

A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: the HALCyon programme

Tamuno Alfred et al. PLoS One. 2012.

Abstract

Background: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.

Methods: As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.

Results: Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82-0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.

Conclusion: Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Pooled Results of Associations between Genotypes and Measures of Anthropometry.
Adjusted for age and sex. Models used: rs35767 (IGF1)- (C/T+T/T) vs. C/C; rs7127900 (IGF2)- (C/T+T/T) vs. C/C; rs2854744 (IGFBP3- per minor (A) allele; rs2943641 (IRS1)- per minor (T) allele; rs2665802 (GH1)- per minor (T) allele; d3GHR- (fl/d3+d3/d3) vs. fl/fl. fl: full length; d3: exon-3 deletion.
Figure 2
Figure 2. Pooled Results of Associations between Genotypes and Grip Strength, TGUG and Chair Rises.
Adjusted for age and sex. Timed chair rises on reciprocal of time taken in sec ×100. Models used: rs35767 (IGF1)- (C/T+T/T) vs. C/C; rs7127900 (IGF2)- (C/T+T/T) vs. C/C; rs2854744 (IGFBP3- per minor (A) allele; rs2943641 (IRS1)- per minor (T) allele; rs2665802 (GH1)- per minor (T) allele; d3GHR- (fl/d3+d3/d3) vs. fl/fl. fl: full length; d3: exon-3 deletion.
Figure 3
Figure 3. Pooled Results of Associations between Genotypes and Poor Balance.
Adjusted for age and sex. Poor balance defined as inability to complete the Flamingo test for 5 s in Boyd Orr, HAS, HCS, NSHD and CaPS, and 5 s of the tandem test in ELSA. Models used: rs35767 (IGF1)- (C/T+T/T) vs. C/C; rs7127900 (IGF2)- (C/T+T/T) vs. C/C; rs2854744 (IGFBP3- per minor (A) allele; rs2943641 (IRS1)- per minor (T) allele; rs2665802 (GH1)- per minor (T) allele; d3GHR- (fl/d3+d3/d3) vs. fl/fl. fl: full length; d3: exon-3 deletion.
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