Association of the ACTN3 Genotype and Physical Functioning With Age in Older Adults

Abstract

Objective The purpose of this study was to examine the association of the alpha-actinin-3 (ACTN3) R577X polymorphism on muscle function and physical performance in older adults. Methods We measured knee extensor torque, midthigh muscle cross-sectional area, muscle quality, short physical performance battery score, and 400-meter walk time at baseline and after 5 years in white older adults aged 70–79 years in the Health, Aging and Body Composition Study cohort (n = 1367). Incident persistent lower extremity limitation (PLL) over 5 years was additionally assessed. We also examined white men in the Osteoporotic Fractures in Men Study, a longitudinal, observational cohort (n = 1152) of men 65 years old or older as a validation cohort for certain phenotypes. Results There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes. Male X-homozygotes had a significantly greater adjusted 5-year increase in their 400-meter walk time compared to R-homozygotes and heterozygotes (p = .03). In women, X-homozygotes had a ~35% greater risk of incident PLL compared to R-homozygotes (hazard ratio = 0.65, 95% confidence interval = 0.44–0.94). There were no other significant associations between any of the phenotypes and ACTN3 genotype with aging in either cohort. Conclusions The ACTN3 polymorphism may influence declines in certain measures of physical performance with aging in older white adults, based on longitudinal assessments. However, the influence of the ACTN3 R577X polymorphism does not appear to have a strong effect on skeletal muscle–related phenotypes based on the strength and consistency of the associations and lack of replication with regard to specific phenotypes.

TheACTN3R577X genotype is associated with muscle function in a Japanese population

“…The present study of a large Japanese cohort confirmed that subjects with the ACTN3 RR or RX genotype possess greater lower-extremity muscle function, which is in agreement with the results of previous studies in the Caucasian population (Walsh et al 2008) and athletes (Yang et al 2003;Kikuchi et al 2013). Delmonico et al (2008) demonstrated that the ACTN3 R577X genotype was associated with a change in the performance phenotype after at least 4 years of aging in a large cohort of elderly subjects. This study suggested that the ACTN3 XX genotype may play a small role in the age-associated decline in 400-m walking time in male subjects and may increase the risk of functional limitation in female subjects.…”

“…However, a meta-analysis by Alfred et al (2011) showed that while the ACTN3 R577X genotype is associated with sprint and power athletic status in Europeans, this genotype does not appear to be associated with muscle phenotypes in the general population. Delmonico et al (2008), in their longitudinal study, reported that the ACTN3 R577X genotype may be associated with a decline in certain measures of physical performance with age, particularly in older populations. However, they also concluded that the ACTN3 R577X genotype does not appear to have a strong effect on muscle phenotypes, based on the strength and consistency of the associations and the lack of replication of specific phenotypes.…”

“…Previous studies have suggested that adults with ACTN3 deficiency may have difficulty maintaining muscle mass and function with age (Delmonico et al 2008), and this deficiency is a risk factor for falls among older Caucasian women (Judson et al 2011). In addition, Seto et al (2011) suggested that ACTN3-deficient individuals may experience a faster decline in muscle function with increasing age, as indicated by the results of studies on ACTN3 knockout mice Seto et al 2011).…”

Secrets of Healthy Aging and Longevity From Exceptional Survivors Around the Globe: Lessons From Octogenarians to Supercentenarians

“…Further addressing this field of inquiry, the final two articles of the Journal also use prospective study designs to assess the potential role of variation in two particular genes and risk for healthy aging and longevity. The first article, that of Delmonico and colleagues (59), examined the association of variation within the alpha-actinin-3 (ACTN3) gene on muscle function and physical performance in older adults. The ACTN3 R577X polymorphism predicted decline in some performance variables with age in men and women.…”

Association of the ACTN3 R577X Polymorphism in Polish Power-Orientated Athletes

“…myostatin gene ( MSTN ), angiotensin converting enzyme gene ( ACE ), peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1 α), hypoxia-inducible factor-1 ( HIF-1 ) and others (Buchner et al, 1993; Spurway and Wackerhage, 2006). Therefore, only a small number of genes containing single nucleotide polymorphisms (SNPs) have been identified as candidate genes for explaining this variability (Delmonico et al, 2008). One of them is alpha-actinin-3 gene ( ACTN3 ), which encodes the protein a-actinin-3.…”