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

Objective: The androgen receptor (AR) gene contains a CAG repeat polymorphism coding for a polyglutamine chain, the length of which is inversely correlated with AR transcriptional activity. We explored whether this polymorphism modulates the activities of testosterone (T) related to body composition in elderly men. Design: We performed cross-sectional analyses using data from a 4-year follow-up study in community-dwelling men aged 75–89 years (n=159). Methods: Body composition was assessed by dual-energy X-ray absorptiometry and its relation with T and the AR gene CAG repeat length was assessed by multiple linear regression analyses, adjusting for confounding and exploring effect modification. Results: AR gene CAG repeat length was not directly related to body composition, either with or without adjustment for confounding variables like age, weight, total T or sex hormone binding globulin (SHBG) levels. However, exploration of effect modification showed that CAG repeat length modulated the relation between T and body composition (standardized regression coefficients of interaction term: β=0.12, P<0.01 and β=−0.09, P<0.05 for fat-free mass and fat mass respectively). These results were confirmed using similar models and data of mean T, SHBG and weight of the 2 years’ preceding body composition assessment instead of data of the same year (β=0.09, P<0.05 and β=−0.09, P<0.05 respectively). Conclusion: These findings suggest that the AR gene CAG polymorphism contributes, albeit modestly, to the between-subject variation of T action on body composition in community-dwelling elderly men.

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Androgen Receptor Gene CAG Repeat Polymorphism in the Development of Ovarian Hyperandrogenism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021791 ◽

2003 ◽

Vol 88 (7) ◽

pp. 3333-3338 ◽

Cited By ~ 103

Author(s):

Lourdes Ibáñez ◽

Ken K. Ong ◽

Nigel Mongan ◽

Jarmo Jääskeläinen ◽

Maria Victoria Marcos ◽

...

Keyword(s):

Androgen Receptor ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Cag Repeat ◽

Repeat Polymorphism ◽

Ovarian Hyperandrogenism

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CAG Repeat Polymorphism in the Androgen Receptor Gene in Women with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110894 ◽

2011 ◽

Vol 39 (1) ◽

pp. 10-17 ◽

Cited By ~ 5

Author(s):

VIOLETTA DZIEDZIEJKO ◽

MATEUSZ KURZAWSKI ◽

KRZYSZTOF SAFRANOW ◽

ANDRZEJ OSSOWSKI ◽

JAROSLAW PIATEK ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Androgen Receptor ◽

White Women ◽

Receptor Gene ◽

Study Groups ◽

Androgen Receptor Gene ◽

Cag Repeat ◽

Cag Repeats ◽

Repeat Polymorphism ◽

Erosive Disease

Objective.Rheumatoid arthritis (RA) is the most common chronic, autoimmune, inflammatory disease, with a genetic and hormonal background. The prevalence of women among patients with RA suggests the important role of sex hormones in the pathogenesis of RA. We examined the association between CAG repeat polymorphism in the androgen receptor (AR) gene and susceptibility to RA and its clinical features in white women.Methods.The study groups consisted of 325 female patients with RA and 238 female controls. CAG repeat polymorphism was determined using polymerase chain reaction and subsequent fragment analysis by capillary electrophoresis.Results.The number of CAG repeats in patients did not differ from that of controls (22.1 ± 2.9 vs 21.9 ± 2.9, respectively; p = 0.26), but the presence of articular erosions was associated with a lower number of repeats in the shorter allele of patients with RA (20.4 ± 2.2 vs 21.2 ± 2.4; p = 0.031). When alleles with < 22 CAG were classified as short (S) and those with ≥ 22 CAG as long (L), the age at diagnosis of RA was lower in women with S-S genotype in comparison to combined S-L + L-L genotypes (43.0 ± 14.6 yrs vs 47.6 ± 12.5 yrs; p = 0.021). In patients with the L-L genotype, the frequency of erosive disease (OR 0.45, 95% CI 0.25–0.80, p = 0.0085) and extraarticular manifestations (OR 0.50, 95% CI 0.26–0.98, p = 0.047) was lower in comparison to carriers of the S allele. In multivariate analysis, the L-L genotype was an independent factor associated with a lower risk of erosions (OR 0.44, 95% CI 0.22–0.90, p = 0.024).Conclusion.The results suggest the association of short AR (CAG)n alleles with earlier onset and a more aggressive course of RA.

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