The association of cytosine-adenine-guanine repeat polymorphism in the androgen receptor gene with nodulocystic acne in Egyptian patients
DOI:
https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20231823Keywords:
Androgen receptors, CAG repeat, Nodulocystic acneAbstract
Background: The role of androgens in acne pathophysiology has been supported by long-standing clinical and experimental observations.
Methods: Genotyping for the androgen receptor gene was performed by PCR-based fragment length analysis, aiming to investigate cytosine-adenine-guanine (CAG) repeat polymorphism in Egyptian nodulocystic acne patients to clarify its relevance to the pathogenesis. Detailed frequency of CAG repeats number in patients and control groups, in 25 males and 25 females and Comparison of CAG repeat number regarding demographic and clinical characteristics was performed.
Results: It was found that females had a higher frequency of longer CAG repeats compared to males, while in control group there was an even distribution of CAG number repeats in both females and males. Male and female acne patients had significantly lower number of CAG repeats compared to controls with statistically significant difference (p≤0.05). Comparison of CAG repeat number regarding demographic and clinical characteristics revealed no significant correlation or association with patients’ age, duration of acne, onset or course of the disease.
Conclusions: These findings support the hypothesis that CAG repeats number affects AR activity, therefore, acne development and severity. Moreover, analysis of CAG repeats number in acne patients can be of considerable importance in the treatment strategy, indicating the role of antiandrogen therapy in acne patients.
References
Degitz K, Ochsendorf F. Pharmacotherapy of acne. Expert Opin Pharmacother. 2008;9(6):955-71.
Chen WC, Zouboulis CC. Hormones and the pilosebaceous unit. Dermato-endocrinol. 2009;1(2):81-6.
Lucky AW. A review of infantile and pediatricacne. Dermatology. 1998;196(1):95-7.
Imperato-McGinley J. 5α-Reductase-2 deficiency and complete androgen insensitivity: lessons from nature. Pediatric Gender Assignment. 2002;44(10):121-34.
Pang Y, He CD, Liu Y, Wang KB, Xiao T, Wang YK, et al. Combination of short CAG and GGN repeats in the androgen receptor gene is associated with acne risk in North East China. J Eur Acad Dermatol Venereol. 2008;22(12):1445-51.
Demirkan S, Sayın DB, Gündüz Ö. CAG polymorphism in the androgen receptor gene in women may be associated with nodulocystic acne. Adv Dermatol Alergol. 2019;36(2):173.
Szabó K, Kemény L. Studying the genetic predisposing factors in the pathogenesis of acne vulgaris. Human Immunol. 2011;72(9):766-73.
Choong CS, Wilson EM. Trinucleotide repeats in the human androgen receptor: a molecular basis for disease. J Mol Endocrinol. 1998;21(3):235-57.
Barros B, Thiboutot D. Hormonal therapies for acne. Clin Dermatol. 2017;35(2):168-72.
Schüring AN, Welp A, Gromoll J, Zitzmann M, Sonntag B, Nieschlag E, Greb RR, Kiesel L. Role of the CAG repeat polymorphism of the androgen receptor gene in polycystic ovary syndrome (PCOS). Exp Clin Endocrinol Diabetes. 2012;120(2):73-9.
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9.
Hacivelioglu S, Gungor AN, Gencer M, Uysal A, Hizli D, Koc E, Cosar E. Acne severity and the Global Acne Grading System in polycystic ovary syndrome. Int J Gynaecol Obstet. 2013;123(1):33-6.
Lichtenberger R, Simpson MA, Smith C, Barker J, Navarini AA. Genetic architecture of acne vulgaris. J Eur Acad Dermatol Venereol. 2017;31(12):1978-90.
Yang Z, Yu H, Cheng B, Tang W, Dong Y, Xiao C, He L. Relationship between the CAG repeat polymorphism in the androgen receptor gene and acne in the Han ethnic group. Dermatology. 2009;218(4):302-6.
Ju Q, Tao T, Hu T, Karadağ AS, Al-Khuzaei S, Chen W. Sex hormones and acne. Clin Dermatol. 2017;35(2):130-7.
Kircik LH. Androgens and acne: perspectives on clascoterone, the first topical androgen receptor antagonist. Expert Opin Pharmacother. 2021;22(13):1801-6.
Plewig G, Melnik B, Chen W. Acne Epidemiology and Genetics. In Plewig and Kligman´ s Acne and Rosacea. 2019;2(2):35-44.
Lai JJ, Chang P, Lai KP, Chen L, Chang C. The role of androgen and androgen receptor in skin-related disorders. Arch Dermatol Res. 2012;304(7):499-510.
Cong TX, Hao D, Wen X, Li XH, He G, Jiang X. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res. 2019;311(5):337-49.
Sawaya ME, Shalita AR. Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopecia, hirsutism, and acne. J Cutan Med Surg. 1998;3(1):9-15.
Qin Z, Li X, Han P, Zheng Y, Liu H, Tang J, et al. Association between polymorphic CAG repeat lengths in the androgen receptor gene and susceptibility to prostate cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2017;96(25):e7258.
Eiras MC, Pinheiro DP, Romcy KAM, Ferriani RA, Reis RMD, Furtado CLM. Polycystic Ovary Syndrome: the Epigenetics Behind the Disease. Reprod Sci. 2022;29(3):680-94.
Tan JSJ, Ong KC, Ong DBL, Wu YS, Razack A, Kuppusamy S, et al. Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer. Malays J Pathol. 2019;41(3):243-51.
Polat S, Karaburgu S, Unluhizarci K, Dündar M, Özkul Y, Arslan YK, Karaca Z, Kelestimur F. The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism. J Endocrinol Invest. 2020;43(9):1271-81.
Van Nieuwerburgh F, Stoop D, Cabri P, Dhont M, Deforce D, De Sutter P. Shorter CAG repeats in the androgen receptor gene may enhance hyperandrogenicity in polycystic ovary syndrome. Gynecol Endocrinol. 2008;24(12):669-73.
Skrgatic L, Baldani DP, Cerne JZ, Ferk P, Gersak K. CAG repeat polymorphism in androgen receptor gene is not directly associated with polycystic ovary syndrome but influences serum testosterone levels. J Steroid Biochem Mol Biol. 2012;128(3-5):107-12.
Keene S, Goren A. Therapeutic hotline. Genetic variations in the androgen receptor gene and finasteride response in women with androgenetic alopecia mediated by epigenetics. Dermatol Ther. 2011;24(2):296-300.
Ghassemi M, Ghaffarpour GH, Ghods S. The effect of GGC and CAG repeat polymorphisms on the androgen receptor gene in response to finasteride therapy in men with androgenetic alopecia. J Res Med Sci. 2019;24:104.
Tirabassi G, Cignarelli A, Perrini S, Delli Muti N, Furlani G, Gallo M, et al. Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action. Int J Endocrinol. 2015;298107.
Berger I, Böhmer F, Ponholzer A, Madersbacher S. Prostate cancer in senior adults: over- or undertreated? Wien Med Wochenschr. 2009;159(21-22):521-8.