Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men

European Journal of Endocrinology

Volumn 161, Issue 1, 2009, Pages 171-177

  Bogaert, Veerle ^a   Vanbillemont, Griet ^a   Taes, Youri ^a   De Bacquer, Dirk ^b   Deschepper, Ellen ^b   Van Steen, Kristel ^b,c,d   Kaufman, Jean Marc ^a  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

^b GHENT UNIVERSITY   (Belgium)

^c UNIVERSITY OF LIÈGE   (Belgium)

^d Statistics and Epidemiology in Genetics Belgium   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; CYSTEINYLALANYLGLYCINE; GLYCYLGLYCYLASPARAGINE; LUTEINIZING HORMONE; TESTOSTERONE; TRIPEPTIDE; UNCLASSIFIED DRUG;

ADULT; AGE; AGED; AMINO ACID SEQUENCE; ARTICLE; BODY MASS; CONTROLLED STUDY; DNA POLYMORPHISM; FEEDBACK SYSTEM; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC TRANSCRIPTION; GENOTYPE; HORMONAL REGULATION; HORMONE ACTION; HUMAN; HUMAN EXPERIMENT; IMMUNOASSAY; LUTEINIZING HORMONE BLOOD LEVEL; MALE; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REGULATORY MECHANISM; TESTOSTERONE BLOOD LEVEL; TESTOSTERONE RELEASE; TRINUCLEOTIDE REPEAT; BLOOD; COHORT ANALYSIS; GENETICS; MIDDLE AGED; MOLECULAR GENETICS; MUTATION; NUCLEOTIDE SEQUENCE; PHENOTYPE;

ADULT; BASE SEQUENCE; COHORT STUDIES; GENOTYPE; HUMANS; LUTEINIZING HORMONE; MALE; MIDDLE AGED; MOLECULAR SEQUENCE DATA; MUTATION; PHENOTYPE; POLYMORPHISM, GENETIC; RECEPTORS, ANDROGEN; TESTOSTERONE; TRINUCLEOTIDE REPEATS; YOUNG ADULT;

EID: 67650712272     PISSN: 08044643     EISSN: 1479683X     Source Type: Journal    
DOI: 10.1530/EJE-09-0123     Document Type: Article

References (31)

1. Albertelli MA, Scheller A, Brogley M & Robins DM. Replacing the mouse androgen receptor with human alleles demonstrates glutamine tract length-dependent effects on physiology and tumorigenesis in mice. Molecular Endocrinology 2006 20 1248-1260.
2. Choong CS, Kemppainen JA, Zhou ZX & Wilson EM. Reduced androgen receptor gene expression with first exon CAG repeat expansion. Molecular Endocrinology 1996 10 1527-1535.
3. Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, Moore NL, Raynor M, Neufing PJ, Coetzee GA & Tilley WD. Structural and functional consequences of glutamine tract variation in the androgen receptor. Human Molecular Genetics 2004 13 1677-1692.
4. Crabbe P, Bogaert V, De Bacquer D, Goemaere S, Zmierczak H & Kaufman JM. Part of the interindividual variation in serum testosterone levels in healthy men reflects differences in androgen sensitivity and feedback set point: contribution of the androgen receptor polyglutamine tract polymorphism. Journal of Clinical Endocrinology and Metabolism 2007 92 3604-3610.
5. Zitzmann M & Nieschlag E. The CAG repeat polymorphism within the androgen receptor gene and maleness. International Journal of Andrology 2003 26 76-83.
6. Chang CS, Kokontis J & Liao ST. Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors. PNAS 1988 85 7211-7215.
7. Brockschmidt FF, Nothen MM & Hillmer AM. The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function. Journal of Molecular Endocrinology 2007 39 1-8.
8. Ding D, Xu L, Menon M, Reddy GP & Barrack ER. Effect of GGC (glycine) repeat length polymorphism in the human androgen receptor on androgen action. Prostate 2005 62 133-139.
9. Gao T, Marcelli M & McPhaul MJ. Transcriptional activation and transient expression of the human androgen receptor. Journal of Steroid Biochemistry and Molecular Biology 1996 59 9-20.
10. Lundin KB, Giwercman A, Dizeyi N & Giwercman YL. Functional in vitro characterisation of the androgen receptor GGN polymorphism. Molecular and Cellular Endocrinology 2007 264 184-187.
11. Werner R, Holterhus PM, Binder G, Schwarz HP, Morlot M, Struve D, Marschke C & Hiort O. The A645D mutation in the hinge region of the human androgen receptor (AR) gene modulates AR activity, depending on the context of the polymorphic glutamine and glycine repeats. Journal of Clinical Endocrinology and Metabolism 2006 91 3515-3520.
12. Buchanan G. Contribution of the androgen receptor to prostate cancer predisposition and progression. Cancer and Metastasis Reviews 2001 20 207-223.
13. Hillmer AM, Hanneken S, Ritzmann S, Becker T, Freudenberg J, Brockschmidt FF, Flaquer A, Freudenberg-Hua Y, Jamra RA, Metzen C, Heyn U, Schweiger N, Betz RC, Blaumeiser B, Hampe J, Schreiber S, Schulze TG, Hennies HC, Schumacher J, Propping P, Ruzicka T, Cichon S, Wienker TF, Kruse R & Nothen MM. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. American Journal of Human Genetics 2005 77 140-148.
14. Lundin KB, Giwercman YL, Rylander L, Hagmar L & Giwercman A. Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men. European Journal of Endocrinology 2006 155 347-354.
15. Aschim EL, Nordenskjold A, Giwercman A, Lundin KB, Ruhayel Y, Haugen TB, Grotmol T & Giwercman YL. Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene. Journal of Clinical Endocrinology and Metabolism 2004 89 5105-5109.
16. Gonzalez A, Javier Dorta F, Rodriguez G, Brito B, Rodriguez MA, Cabrera A, Diaz-Chico JC, Reyes R, Aguirre-Jaime A & Nicolas Diaz-Chico B. Increased risk of breast cancer in women bearing a combination of large CAG and GGN repeats in the exon 1 of the androgen receptor gene. European Journal of Cancer 2007 43 2373-2380.
17. Giwercman YL, Abrahamsson P, Giwercman A, Gadaleanu V & Ahlgren G. The 5 alpha-reductase type II A49T and V89L high-activity allelic variants are more common in men with prostate cancer compared with the general population. European Urology 2005 48 679-685.
18. Bogaert V, Taes Y, Konings P, Van Steen K, De Bacquer D, Goemaere S, Zmierczak H, Crabbe P & Kaufman JM. Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings. Clinical Endocrinology 2008 69 129-135.
19. Coetsier P, De Backer G, De Corte W & Kornitzer M. Belgian job stress study (BELSTRESS): overview of the study model and research methods. Revue de Psychologie et de Psychométrie 1996 17 17-35.
20. Goemaere S, Van Pottelbergh I, Zmierczak H, Toye K, Daems M, Demuynck R, Myny H, De Bacquer D & Kaufman JM. Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: no major role of sex steroid status. Bone 2001 29 286-291.
21. Van Den Saffele JK, Goemaere S, De Bacquer D & Kaufman JM. Serum leptin levels in healthy ageing men: are decreased serum testosterone and increased adiposity in elderly men the consequence of leptin deficiency? Clinical Endocrinology 1999 51 81-88.
22. Mahmoud AM, Goemaere S, El-Garem Y, Van Pottelbergh I, Comhaire FH & Kaufman JM. Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men. Journal of Clinical Endocrinology and Metabolism 2003 88 179-184.
23. Vermeulen A, Verdonck L & Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. Journal of Clinical Endocrinology and Metabolism 1999 84 3666-3672.
24. Kaufman JM & Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocrine Reviews 2005 26 833-876.
25. Stanford J. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Research 1997 57 1194-1198.
26. Hakimi J. Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. Clinical Cancer Research 1997 3 1599-1608.
27. Edwards S. Androgen receptor polymorphisms: association with prostate cancer risk, relapse and overall survival. International Journal of Cancer 1999 84 458-465.
28. Suter NM, Malone KE, Daling JR, Doody DR & Ostrander EA. Androgen receptor (CAG)n and (GGC)n polymorphisms and breast cancer risk in a population-based case-control study of young women. Cancer Epidemiology, Biomarkers and Prevention 2003 12 127-135.
29. Lumbroso R. Codon-usage variants in the polymorphic (GGN)(n) trinucleotide repeat of the human androgen receptor gene. Human Genetics 1997 101 43-46.
30. Lundin K. No association between mutations in the human androgen receptor GGN repeat and inter-sex conditions. Molecular Human Reproduction 2003 9 375-379.
31. Komar AA, Lesnik T & Reiss C. Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation. FEBS Letters 1999 462 387-391.