Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men?

Lapauw, Bruno; Goemaere, Stefan; Crabbe, Patricia; Kaufman, Jean; Ruige, Johannes

doi:10.1530/eje-06-0607

Cited by 38 publications

(36 citation statements)

References 40 publications

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“…These results and previous observations (14,15,(23)(24)(25)32) support the concept that serum testosterone and indicators of AR sensitivity should be studied simultaneously with respect to sex-dimorphic traits and behaviours.…”

Section: Conclusion and Discussionsupporting

confidence: 88%

“…Some studies have already documented these interactions. It was found, for example, that the AR gene CAG polymorphism contributed modestly to the between-subject variation in testosterone action on body composition in community-dwelling elderly individuals (23). In addition, it has been shown that the CAG repeat polymorphism modulates responses induced by testosterone replacement therapy in hypogonadal men (24,25).…”

Section: Introductionmentioning

confidence: 99%

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Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males

Vermeersch¹,

T’Sjoen²,

Kaufman³

et al. 2010

European Journal of Endocrinology

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Objectives: Androgen activity has been implicated in a range of traits and behaviours that have well-documented sex differences. However, the results of the studies on the relationship between testosterone and these traits and behaviours are inconsistent. This study has analyzed i) whether CAG repeat length, a presumed modulator of androgen receptor sensitivity, is associated with sex-dimorphic traits and behaviours (aggressive and non-aggressive risk-taking (ART and NART), dominance, depressive symptoms and self-esteem), and ii) whether CAG repeat length interacts with free testosterone (FT) with respect to these traits and behaviours. Design and methods: Data obtained from a group of adolescent boys (nZ301; mean age: 14.4 years) were analyzed using multivariate general linear modelling (SPSS, Chicago, IL, USA 15.0). Results: We found no direct correlation between CAG repeat length and dependent variables. We found significant interactions between CAG repeat length and testosterone, indicating that FT was more positively related to ART and NART with a shorter repeat length, and that an inverse association of FT with depressive symptoms and a positive association with self-esteem were stronger in boys with a longer CAG repeat length. Conclusion: Our findings indicate the importance of studying FT and CAG repeat length simultaneously with respect to sex-dimorphic traits, taking into account the possible interactions between the two.

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Section: Conclusion and Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males

Vermeersch¹,

T’Sjoen²,

Kaufman³

et al. 2010

European Journal of Endocrinology

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“…However, other studies reported no association of CAG repeat length with body composition (Lapauw et al 2007) or with physical performance in old men (Kenny et al 2005).…”

Section: Cross-sectional Genetic Association Studiesmentioning

confidence: 90%

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

Garatachea

Lucía

2011

AGE

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Western populations are living longer. Ageing decline in muscle mass and strength (i.e. sarcopenia) is becoming a growing public health problem, as it contributes to the decreased capacity for independent living. It is thus important to determine those genetic factors that interact with ageing and thus modulate functional capacity and skeletal muscle phenotypes in older people. It would be also clinically relevant to identify 'unfavourable' genotypes associated with accelerated sarcopenia. In this review, we summarized published information on the potential associations between some genetic polymorphisms and muscle phenotypes in older people. A special emphasis was placed on those candidate polymorphisms that have been more extensively studied, i.e. angiotensinconverting enzyme (ACE) gene I/D, α-actinin-3 (ACTN3) R577X, and myostatin (MSTN) K153R, among others. Although previous heritability studies have indicated that there is an important genetic contribution to individual variability in muscle phenotypes among old people, published data on specific gene variants are controversial. The ACTN3 R577X polymorphism could influence muscle function in old women, yet there is controversy with regards to which allele (R or X) might play a 'favourable' role. Though more research is needed, up-to-date MSTN genotype is possibly the strongest candidate to explain variance among muscle phenotypes in the elderly. Future studies should take into account the association between muscle phenotypes in this population and complex gene-gene and gene-environment interactions.

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“…Although controversial findings existed,3435 androgen receptor CAG repeat polymorphism has been found to be involved in determining inter-individual variability of circulating testosterone and SHBG level, probably through negative feedback mechanism 363738. Ackerman et al 39.…”

Section: Discussionmentioning

confidence: 99%

Genetic effects on serum testosterone and sex hormone-binding globulin in men: a Korean twin and family study

Sung

Song

2016

Asian J Androl

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We conducted a community-based cross-sectional study to evaluate the role of genetics in determining the individual difference in total testosterone and sex hormone-binding globulin levels. Study participants comprised 730 Korean men consisting of 142 pairs of monozygotic twins, 191 pairs of siblings, and 259 father-offspring pairs from 270 families who participated in the Healthy Twin study. Serum concentration of total testosterone and sex hormone-binding globulin were measured by chemiluminescence immunoassay, and free testosterone and bioavailable testosterone were calculated using Vermeulen's method. Quantitative genetic analysis based on a variance decomposition model showed that the heritability of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin were 0.56, 0.45, 0.44, and 0.69, respectively after accounting for age and body mass index. Proportions of variance explained by age and body mass index varied across different traits, from 8% for total testosterone to 31% for sex hormone-binding globulin. Bivariate analysis showed a high degree of additive genetic correlation (ρG = 0.67) and a moderate degree of individual-specific environmental correlation (ρE = 0.42) between total testosterone and sex hormone-binding globulin. The findings confirmed the important role of genetics in determining the individually different levels of testosterone and sex hormone-binding globulin during adulthood in Korean men as found in non-Asian populations, which may suggest that common biologic control for determining testosterone level directly or indirectly through binding protein are largely shared among different populations.

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Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men?

Cited by 38 publications

References 40 publications

Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males

Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males

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

Genetic effects on serum testosterone and sex hormone-binding globulin in men: a Korean twin and family study

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