Physical Function Is Weakly Associated with Angiotensin-Converting Enzyme Gene I/D Polymorphism in Elderly Japanese Subjects

Abstract

Background: The turning point in the deterioration of physical function seems to occur between the ages of 70 and 80 years. In particular, muscle strength may decline even more in subjects older than 75. A recent study found that the angiotensin-converting enzyme (ACE) genotype also affects physiological left ventricular hypertrophy. A very limited number of papers have examined genetic differences in resistance and endurance forms of a single sporting discipline. Objective: The purpose of this study was to evaluate the relationship between ACE genotype and physical function by controlling the known confounding factors including dental status. Methods:We selected 431 subjects who were aged 76 years and did not require special care for their daily activities. We conducted a medical examination, followed by 5 physical function tests, as follows: (1) maximum hand grip strength, (2) maximal isometric knee extensor strength, (3) maximal stepping rate for 10 s, (4) one-leg standing time with eyes open and (5) 10-meter maximum walking speed. Subjects were genotyped for the ACE intron 16 Alu insertion. In addition, serum concentrations of total cholesterol, total protein, IgA and IgG were measured at a commercial laboratory. The Eichner index was used as an indicator of occlusal condition. Multiple linear regression analysis was performed to evaluate the relationship between the ACE gene insertion/deletion (I/D) polymorphism and physical function considering confounding factors. Results: The ACE gene I/D polymorphism was positively associated with hand grip strength and 10-meter maximum walking speed. Betas of hand grip strength were 0.09 for I/D (p = 0.022) and 0.12 for insertion/insertion (I/I; p = 0.004). Betas of 10-meter walking speed were –0.11 for I/D (p = 0.093) and –0.14 for I/I (p = 0.039). Dental status such as Eichner index class C was significantly associated with one-leg standing time with eyes open (beta –0.11; p = 0.028). Conclusion: This study suggests that there is a significant relationship between ACE genotype and physical function. In particular, subjects with the ACE deletion/deletion genotype were associated with upper extremities.

Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients

“…Our results suggested the ACE I/I genotype was a possible marker for ADL disability, particularly in men. At present, previous studies addressing the role of ACE genotypes in functional decline or in decline of physical performances in older people showed inconclusive results (Frederiksen et al 2003a, b;Kritchevsky et al 2005;Giaccaglia et al 2008;Yoshihara et al 2009). In a 2-year follow-up study on elderly Danish twins, ACE genotypes were not associated with physical abilities, determined by means of ADL score and questions about demanding activities, such as running or cognitive function (Frederiksen et al 2003a).…”

“…The current findings appear to contradict some previous reports of association between the I/I genotype and improved endurance or function. Yet the findings of other studies in older adults including those of response to exercise in wellfunctioning older adults (Kritchevsky et al 2005), of greater gains in knee extensor strength (Giaccaglia et al 2008), and of improved hand-grip strength (Yoshihara et al 2009) all associated with the ACE D/D genotype also contradict other areas of the literature in which ACE has been implicated with forms of arthritis (Veale et al 1992;Dalbeth and Haskard, 2005).…”

“…Finally, a recent study on Japanese older subjects found a significant relationship between ACE genotype and physical function. In particular, the ACE D/D genotype was associated with hand-grip strength that evaluated physical function in the upper extremities (Yoshihara et al 2009), although these findings can only be generalized cautiously and could not be applied to non-Asian populations (Sagnella et al 1999). The suggested improved physical function and disability after exercise in older subjects linked to the presence of the ACE D/D genotype or D allele (Kritchevsky et al 2005;Giaccaglia et al 2008), and the cross-sectional association of D/D genotype with physical function in older Japanese (Yoshihara et al 2009) confirmed the findings of the present study in which the ACE I/I genotype was associated to ADL disability.…”

“…In fact, the D allele has been associated with increased muscle strength and power, whereas the I allele has been associated with improved muscular endurance (Gayagay et al 1998;Myerson et al 1999;Williams et al 2000;Charbonneau et al 2008) and cardio-respiratory performances (Guazzi et al 1999a, b;Payne and Montgomery, 2003;Tsianos et al 2004;Thompson et al 2007). However, data indicating an association between the ACE I/D polymorphism and functional decline or physical performance in older adults are still under debate (Frederiksen et al 2003a, b;Kritchevsky et al 2005;Giaccaglia et al 2008;Yoshihara et al 2009). Indeed, the mechanisms for the interesting findings on muscle performance and endurance remain unclear although some hypotheses have been suggested to include altered substrate delivery in subjects as a result of modulated cardiac output and muscle vascularisation (Montgomery et al 1998), both of which ACE could mediate as a result of its role in the formation of the angiogenic and vasoactive angiotensin II peptide (de Resende et al 2010).…”

Genes and the ageing muscle: a review on genetic association studies

“…Yoshihara and co-workers studied the relationship of the ACE I/ D variation with muscle and fitness phenotypes in old Japanese men and women who did not require special care for their daily activities (Yoshihara et al 2009). They found the ACE I/D polymorphism to be associated with handgrip strength and 10-m maximum walking speed, but not with leg muscle extensor strength.…”