No evidence that 2D:4D is related to the number of CAG repeats in the androgen receptor gene

Frontiers in Endocrinology

Volumn 4, Issue DEC, 2013, Pages

  Hönekopp, Johannes ^a  

^a NORTHUMBRIA UNIVERSITY   (United Kingdom)

Author keywords

2D:4D; AR gene; CAG repeats; Meta analysis; Testosterone

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; MARKER; TESTOSTERONE;

ANDROGEN RECEPTOR GENE; ARTICLE; CAG REPEAT; CORRELATION ANALYSIS; GENE; GENE ACTIVATION; GENETIC TRANSCRIPTION; HUMAN; META ANALYSIS;

EID: 84892162400     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2013.00185     Document Type: Article

References (57)

1. Hines M. Gender development and the human brain. Annu Rev Neurosci (2011) 34:69-88. doi:10.1146/annurev-neuro-061010-113654.
2. Cohen-Bendahan CCC, van de Beek C, Berenbaum SA. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings. Neurosci Biobehav Rev (2005) 29:353-84. doi:10.1016/j.neubiorev.2004.11.004.
3. Manning JT. Resolving the role of prenatal sex steroids in the development of digit ratio. Proc Natl Acad Sci U S A (2012) 108:16143-4. doi:10.1073/pnas.1113312108.
4. Berenbaum SA, Bryk KK, Nowak N, Quigley CA, Moffat S. Fingers as a marker of prenatal androgen exposure. Endocrinology (2009) 150:4819-22. doi:10.1210/en.2009-0774.
5. Breedlove SM. Organizational hypothesis: instances of the fingerpost. Endocrinology (2010) 151:4116-22. doi:10.1210/en.2010-0041.
6. Dean A, Sharpe RM. Anogenital distance or digit length ratio as measures of fetal androgen exposure: relationship to male reproductive development and its disorders. J Clin Endocrinol Metab (2013) 98:2230-8. doi:10.1210/jc.2012-4057.
7. Zheng Z, Cohn MJ. Developmental basis of sexually dimorphic digit ratios. Proc Natl Acad Sci U S A (2011) 108:16289-94. doi:10.1073/pnas.1108312108.
8. Lutchmaya S, Baron-Cohen S, Raggatt P, Knickmeyer R, Manning JT. 2nd to 4th digit ratios, fetal testosterone and estradiol. Early Hum Dev (2004) 77:23-8. doi:10.1016/j.earlhumdev.2003.12.002.
9. Hönekopp J, Watson S. Meta-Analysis of digit ratio 2D:4D shows greater sex difference in the right hand. Am J Hum Biol (2010) 22:619-30. doi:10.1002/ajhb.21054.
10. Manning JT, Kilduff LP, Trivers R. Digit ratio (2D:4D) in Klinefelter's syndrome. Andrology (2013) 1:94-9. doi:10.1111/j.2047-2927.2012.00013.x.
11. Galis F, Ten Broek CMA, Van Dongen S, Wijnaendts LCD. Sexual dimorphism in the prenatal digit ratio (2D:4D). Arch Sex Behav (2010) 39:57-62. doi:10.1007/s10508-009-9485-7.
12. Malas MA, Dogan S, Evcil EH, Desdicioglu K. Fetal development of the hand, digits and digit ratio (2D:4D). Early Hum Dev (2006) 82:469-75. doi:10.1016/j.earlhumdev.2005.12.002.
13. Trivers R, Manning J, Jacobson A. A longitudinal study of digit ratio (2D:4D) and other finger ratios in Jamaican children. Horm Behav (2006) 49:150-6. doi:10.1016/j.yhbeh.2005.05.023.
14. Hönekopp J, Bartholdt L, Beier L, Liebert A. Second to fourth digit length ratio (2D:4D) and adult sex hormone levels: new data and a meta-analytic review. Psychoneuroendocrinology (2007) 32:313-21. doi:10.1016/j.psyneuen.2007.01.007.
15. Muller DC, Giles GG, Manning JT, Hopper JL, English DR, Severi G. Second to fourth digit ratio (2D:4D) and concentrations of circulating sex hormones in adulthood. Reprod Biol Endocrinol (2011) 9:57. doi:10.1186/1477-7827-9-57.
16. Hampson E, Sankar JS. Re-examining the Manning hypothesis: androgen receptor polymorphism and the 2D:4D digit ratio. Evol Hum Behav (2012) 33:557-61. doi:10.1016/j.evolhumbehav.2012.02.003.
17. Manning JT, Bundred PE, Newton DJ, Flanagan BF. The second to fourth digit ratio and variation in the androgen receptor gene. Evol Hum Behav (2003) 24:399-405. doi:10.1016/S1090-5138(03)00052-7.
18. Baculescu N. The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS. J Med Life (2013) 6:18-25.
19. Zitzmann M, Nieschlag E. The CAG repeat polymorphism within the androgen receptor gene and maleness. Int J Androl (2003) 26:76-83. doi:10.1046/j.1365-2605.2003.00393.x.
20. Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, et al. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet (2004) 13:1677-92. doi:10.1093/hmg/ddh181.
21. Beilin J, Ball EMA, Favaloro JM, Zajac JD. Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol (2000) 25:85-96. doi:10.1677/jme.0.0250085.
22. Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res (1994) 22:3181-6. doi:10.1093/nar/22.15.3181.
23. Ding D, Xu L, Menon M, Reddy JPV, Barrack ER. Effect of a short CAG (glutamine) repeat on human androgen receptor function. Prostate (2004) 58:23-32. doi:10.1002/pros.10316.
24. Callewaert L, Christiaens V, Haelens A, Verrijdt G, Verhoeven G, Claessens F. Implications of a polyglutamine tract in the function of the human androgen receptor. Biochem Biophys Res Commun (2003) 306:46-52. doi:10.1016/S0006-291X(03)00902-1.
25. Irvine RA, Ma H, Yu MC, Ross RK, Stallcup MR, Coetzee GA. Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length. Hum Mol Genet (2000) 9:267-74. doi:10.1093/hmg/9.2.267.
26. Kazemi-Esfarjani P, Trifiro MA, Pinsky L. Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. Hum Mol Genet (1995) 4:523-7. doi:10.1093/hmg/4.4.523.
27. Butovskaya ML, Vasilyev VA, Lazebny OE, Burkova VN, Kulikov AM, Mabulla A, et al. Aggression, digit ratio, and variation in the androgen receptor, serotonin transporter and dopamine D4 receptor genes in African foragers: the Hadza. Behav Genet (2012) 42:647-62. doi:10.1007/s10519-012-9533-2.
28. Zhang C, Dang J, Pei L, Guo M, Zhu H, Qu L, et al. Relationship of 2D:4D finger ratio with androgen receptor CAG and GGN repeat polymorphism. Am J Hum Biol (2013) 25:101-6. doi:10.1002/ajhb.22347.
29. Knickmeyer RC, Woolson S, Hamer RM, Konneker T, Gilmore JH. 2D:4D ratios in the first 2 years of life: stability and relation to testosterone exposure and sensitivity. Horm Behav (2011) 60:256-63. doi:10.1016/j.yhbeh.2011.05.009.
30. Loehlin JC, Medland SE, Martin NG. Is CAG sequence length in the androgen receptor gene correlated with finger-length ratio? Pers Indiv Differ (2012) 52:224-7. doi:10.1016/j.paid.2011.09.009.
31. Hurd PL, Vaillancourt KL, Dinsdale NL. Aggression, digit ratio and variation in androgen receptor and monoamine oxidase a genes in men. Behav Genet (2010) 41:543-56. doi:10.1007/s10519-010-9404-7.
32. Schmidt FL, Oh IS, Hayes TL. Fixed-versus random-effects models in meta-analysis: model properties and an empirical comparison of differences in results. Br J Math Stat Psychol (2009) 62:97-128. doi:10.1348/000711007X255327.
33. Folland JP, McCauley TM, Phypers C, Hanson B, Mastana SS. Relationship of 2D:4D finger ratio with muscle strength, testosterone, and androgen receptor CAG repeat genotype. Am J Phys Anthropol (2012) 148:81-7. doi:10.1002/ajpa.22044.
34. Mas M, Alonso C, Hernandez P, Fernandez M, Gutierrez P, Salido E, et al. Androgen receptor CAG and GGN polymorphisms and 2D:4D finger ratio in male to female transsexuals. J Sex Med (2009) 6(Suppl 5):419-20.
35. Cumming G. Understanding the New Statistics. Effect Sizes, Confidence Intervals, and Meta-Analysis. New York: Routledge (2012).
36. 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. J Clin Endocrinol Metab (2007) 92:3604-10. doi:10.1210/jc.2007-0117.
37. Huhtaniemi IT, Pye SR, Limer KL, Thomson W, O'Neill TW, Platt H, et al. Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats. J Clin Endocrinol Metab (2009) 94:277-84. doi:10.1210/jc.2008-0848.
38. Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male Infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab (2007) 92:4319-26. doi:10.1210/jc.2007-1110.
39. Morales A. Androgen replacement therapy and prostate safety. Eur Urol (2002) 41:113-20. doi:10.1016/S0302-2838(01)00039-2.
40. Randall VA. Physiology and pathophysiology of androgenetic Alopecia. Dermatol Ther (2008) 21:314-28. doi:10.1111/j.1529-8019.2008.00214.x.
41. Wang R, Goodarzi MO, Xiong T, Wang D, Azziz R, Zhang H. Negative association between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome? A systematic review and meta-analysis. Mol Hum Reprod (2012) 18:498-509. doi:10.1093/molehr/gas024.
42. Gu M, Dong X, Zhang X, Niu W. The CAG repeat polymorphism of androgen receptor gene and prostate cancer: a meta-analysis. Mol Biol Rep (2012) 39:2615-24. doi:10.1007/s11033-011-1014-9.
43. Zhuo FL, Xu W, Wang L, Wu Y, Xu ZL, Zhao JY. Androgen receptor gene polymorphisms and risk for androgenetic alopecia: a meta-analysis. Clin Exp Dermatol (2012) 37:104-11. doi:10.1111/j.1365-2230.2011.04186.x.
44. Woodhouse LJ, Reisz-Porszasz S, Javanbakht M, Storer TW, Lee M, Zerounian H, et al. Development of models to predict anabolic response to testosterone administration in healthy young men. Am J Physiol Endocrinol Metab (2003) 284:E1009-17. doi:10.1152/ajpendo.00536.2002.
45. Campbell BC, Gray PB, Eisenberg DTA, Ellison P, Sorenson MD. Androgen receptor CAG repeats and body composition among Ariaal men. Int J Androl (2007) 32:140-8. doi:10.1111/j.1365-2605.2007.00825.x.
46. Guadalupe-Grau A, Rodríguez-González FG, Dorado C, Olmedillas H, Fuentes T, Pérez-Gómez J. Androgen receptor gene polymorphisms lean mass and performance in young men. Br J Sports Med (2011) 45:95-100. doi:10.1136/bjsm.2009.060285.
47. Lapauw B, Goemaere S, Crabbe P, Kaufman JM, Ruige JB. Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men? Eur J Endocrinol (2007) 156:395-401. doi:10.1530/EJE-06-0607.
48. Voorhoeve PG, van Mechelen W, Uitterlinden AG, Delemarre-van de Waal HA, Lamberts SWJ. Androgen receptor gene CAG repeat polymorphism in longitudinal height and body composition in children and adolescents. Clin Endocrinol (2011) 74:732-5. doi:10.1111/j.1365-2265.2011.03986.x.
49. Walsh S, Zmuda JM, Cauley JA, Shea PR, Metter EJ, Hurley BF, et al. Androgen receptor CAG repeat polymorphism is associated with fat-free mass in men. J Appl Physiol (2005) 98:132-7. doi:10.1152/japplphysiol.00537.2004.
50. Bennett M, Manning JT, Cook CJ, Kilduff LP. Digit ratio (2D:4D) and performance in elite rugby players. J Sports Sci (2010) 28:1415-21. doi:10.1080/02640414.2010.510143.
51. Hönekopp J, Schuster M. A meta-analysis on 2D:4D and athletic prowess: substantial relationships but neither hand out-predicts the other. Pers Individ Dif (2010) 48:4-10. doi:10.1016/j.paid.2009.08.009.
52. Kilduff LP, Cook CJ, Manning JT. Digit ratio (2D:4D) and performance in male surfers. J Strength Cond Res (2011) 25:3175-80. doi:10.1519/JSC.0b013e318212de8e.
53. Longman D, Stock JT, Wells JCK. Digit Ratio (2D:4D) and rowing ergometer performance in males and females. Am J Phys Anthropol (2011) 144:337-41. doi:10.1002/ajpa.21407.
54. Voracek M, Reimer B, Dressler SG. Digit ratio (2D:4D) predicts sporting success among female fencers independent from physical, experience, and personality factors. Scand J Med Sci Sports (2010) 20:853-60. doi:10.1111/j.1600-0838.2009.01031.x.
55. Forstmeier W, Mueller JC, Kampenaers B. A polymorphism in the oestrogen receptor gene explains covariance between digit ratio and mating behaviour. Proc R Soc Lond B Biol Sci (2010) 277:3353-61. doi:10.1098/rspb.2010.1007.
56. Medland SE, Zayats T, Glaser B, Nyholt DR, Gordon SD, Wright MJ, et al. A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure. Am J Hum Genet (2010) 86:519-25. doi:10.1016/j.ajhg.2010.02.017.
57. Lawrance-Owen AJ, Bargary G, Bosten JM, Goodbourn PT, Hogg RE, Mollon JD. Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio. Hum Genet (2013) 132:415-21. doi:10.1007/s00439-012-1259-y.