Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility

Wallerand, Hervé; Remy-Martin, A.; Chabannes, É.; Bermont, Laurent; Adessi, G. L.; Bittard, Hugues

doi:10.1016/s0015-0282(01)01987-2

Cited by 56 publications

(56 citation statements)

References 20 publications

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“…These results were consistent with other studies in which no association was found (Dadze et al, 2000;Sasagawa et al, 2001;Van Golde et al, 2002;Rajpert-De Meyts et al, 2002;Lund et al, 2003;Martinez-Garza et al, 2008;Badran et al, 2009), but discordant with other studies that did find associations (Tut et al, 1997;Komori et al, 1999;Dowsing et al, 1999;Yoshida et al, 1999;Mifsud et al, 2001;Patrizio et al, 2001;Wallerand et al, 2001;Mengual et al, 2003;Katagiri et al, 2006). However, for CAG repeats >23, risks of >1.2-fold and >1.8-fold were found in azoospermia and severe oligospermia compared to the controls, although CAG repeat length was not significantly correlated with sperm counts in azoospermia and severe oligospermia.…”

Section: Discussionsupporting

confidence: 88%

“…Previous studies on CAG repeats in infertile men have reported conflicting results. Some suggested no expansion (Dadze et al, 2000;Sasagawa et al, 2001;Van Golde et al, 2002;Rajpert-De Meyts et al, 2002;Lund et al, 2003;MartinezGarza et al, 2008;Badran et al, 2009), while others reported increased length (but still within the normal range) with respect to controls (Tut et al, 1997;Dowsing et al, 1999;Yoshida et al, 1999;Mifsud et al, 2001;Patrizio et al, 2001;Wallerand et al, 2001;Mengual et al, 2003;Katagiri et al, 2006). Only one study indicated that reduced CAG repeats are closely associated with impaired spermatogenesis in infertile men (Komori et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene

Han¹,

Jing²,

Ding³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Chromosome abnormalities, Y-chromosome microdeletions, and androgen receptor gene CAG and GGN repeat polymorphisms in infertile Chinese men featuring severe oligospermia and azoospermia were analyzed. Ninety-six fertile men and 189 non-obstructive infertile men, including 125 patients with azoospermia and 64 with severe oligozoospermia, were studied. Seventeen infertile men (9.0%) carried a chromosome abnormality. Twenty (10.6%) carried a Y-chromosome microdeletion. In the remainder of the patients and controls, GGN and CAG repeats were sequenced. Short GGN repeats (n < 23) appeared to be associated with defective spermatogenesis, with the number of GGN repeats strongly correlated with sperm counts. No significant difference in CAG repeats was found between patients and con- trols, nor were CAG repeats correlated with sperm counts. However, for CAG repeats ranging between 24 and 25, there was a >2.5-fold risk (OR = 2.539, 95%CI = 1.206-5.344, P < 0.05) of severe oligospermia and azoospermia. Our results confirmed the significant role of chromosome abnormalities, Y-chromosome microdeletions, and GGN repeats in Chinese male infertility.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene

Han¹,

Jing²,

Ding³

et al. 2013

Genet. Mol. Res.

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“…Similar associations have been observed in previous studies of our team (Lazaros et al, 2008;Lazaros et al, 2011), analyzing the AR(CAG) n and CYP19(TTTA) n polymorphisms separately in other smaller Greek Caucasian populations. Concerning AR(CAG) n , short AR(CAG) n allele carriers had lower sperm motility than long AR(CAG) n allele carriers in both normozoospermic and oligozoospermic groups (Lazaros et al, 2008), while previous studies conducted in European populations observed no association with sperm concentration (Giwercman et al, 1998;Hiort et al, 1999;Dadze et al, 2000;Wallerand et al, 2001;Rajpert-De Meyts et al, 2002;Van Golde et al, 2002;Lund et al, 2003). Short AR(CAG) n alleles are potential risk factors of prostate cancer (Giovannucci et al, 1997;Hsing et al, 2000), and have been shown to result in enhanced AR transcriptional activity both in vivo and in vitro (Chamberlain et al, 1994;Choong et al, 1996).…”

Section: Discussionmentioning

confidence: 79%

Semen quality is influenced by androgen receptor and aromatase gene synergism

et al. 2012

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study question: Does synergism between AR(CAG) n and CYP19(TTTA) n polymorphisms influence the quality of sperm? summary answer: AR(CAG) n and CYP19(TTTA) n polymorphisms had a synergistic effect on sperm concentration and motility. what is known already: Androgens exert their action in the testicular tissue by binding to androgen receptor (AR), while their action is mediated by the aromatase P450 enzyme (CYP19). AR(CAG) n alleles are associated with sperm motility and CYP19(TTTA) n allelic variants have implications for sperm concentration and motility. study design, size, duration: Two hundred oligozoospermic and 250 normozoospermic men who presented for infertility investigation were examined during a period of 2 years.participants/materials, setting, methods: Conventional semen analysis was performed. DNA was extracted from spermatozoa and both polymorphisms were genotyped by polymerase chain reaction. Serum hormone levels were determined.main results and the role of chance: Six combined genotypes were identified between the 18 AR(CAG) n alleles with 12 -32 repeats and the 6 CYP19(TTTA) n alleles with 7-12 repeats. A gradual reduction in the sperm concentration (10 6 /ml) and motility (%) from long AR allele -non-CYP19(TTTA) 7 allele carriers to long AR allele -CYP19(TTTA) 7 homozygotes and from short AR allele -non-CYP19(TTTA) 7 carriers to short AR allele -CYP19(TTTA) 7 homozygotes was observed in normozoospermic men (means + SD; concentration: 93 + 53.1 versus 65 + 48.6 and 85 + 60.1 versus 37 + 17.2l, P , 0.002; motility: 63 + 10.3 versus 55 + 14.5 and 52 + 19.6 versus 41 + 13.7, P , 0.001, respectively). Similar associations were observed in oligozoospermic men (concentration: 10 + 4.2 versus 9 + 5.9 and 10 + 6.3 versus 6 + 3.1, P , 0.03; motility: 47 + 17.1 versus 39 + 6.2 and 39 + 22 versus 27 + 18.3, P , 0.003, respectively). The above associations of the combined genotypes with sperm concentration and motility were confirmed in the total study population (P , 0.006 and P , 0.001, respectively).limitations, reasons for caution: Our study population was limited to Greek Caucasian adult males, residents of Northwest Greece.wider implications of the findings: The confirmation of our findings in other populations would verify the significance of AR and CYP19 genes for spermatogenesis.

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“…Based on this information, in a study of exon 1 of the AR gene in infertile males of predominantly (60%) Chinese ethnic origin it was found that expansion of the trinucleotide (CAG) repeat and thus of the polyglutamine tract could be associated with increased risk of impaired spermatogenesis (Tut et al 1997). This finding was then corroborated by several studies from a variety of different ethnic populations including Japanese, Caucasian, North American, French, Israeli, Taiwanese and Spanish (Yoshida et al 1999;Dowsing et al 1999;Mifsud et al 2001;Wallerand et al 2001;Patrizio et al 2001;Madgar et al 2002;Pan et al 2002;Casella et al 2003;Asatiani et al 2003;Mengual et al 2003). However, several others, who have investigated Swedish, Belgian, German, Japanese, Danish, Dutch, Indian, Greek, New Zealander, Finish, Hong Kong Chinese and Italian populations were unable to demonstrate an association (Giwercman et al 1998;Legius et al 1999;Hiort et al 1999;Dadze et al 2000;Sasagawa et al 2000Sasagawa et al , 2001Von Eckardstein et al 2001;Yu and Handelsman 2001;Kukuvitis et al 2002;Rajpert-De Meyts et al 2002;Van Golde et al 2002;Thangaraj et al 2002;Dhillon and Husain 2003;Erasmuson et al 2003;Lund et al 2003;Tse et al 2003;Ferlin et al 2004).…”

Section: Discussionmentioning

confidence: 88%

“…decade (Tut et al 1997;Yoshida et al 1999;Dowsing et al 1999;Mifsud et al 2001;Patrizio et al 2001;Wallerand et al 2001;Madgar et al 2002;Pan et al 2002;Asatiani et al 2003;Casella et al 2003;Mengual et al 2003), whereas several others were unable to demonstrate an association (Giwercman et al 1998;Hiort et al 1999;Legius et al 1999;Dadze et al 2000;Sasagawa et al 2000Sasagawa et al , 2001Von Eckardstein et al 2001;Yu and Handelsman 2001;Rajpert-De Meyts et al 2002;Van Golde et al 2002;Thangaraj et al 2002;Kukuvitis et al 2002;Erasmuson et al 2003;Dhillon and Husain 2003;Lund et al 2003;Tse et al 2003;Ferlin et al 2004). Thus, the ethnic background of the population studied may play an important role in the correlation between CAG repeat length and male infertility.…”

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confidence: 99%

No Association of the CAG Repeat Length in Exon 1 of the Androgen Receptor Gene with Idiopathic Infertility in Turkish Men: Implications and Literature Review

Tufan

Şatıroğlu-Tufan

Aydınuraz³

et al. 2005

Tohoku J. Exp. Med.

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While the correlation between the CAG repeat length of the androgen receptor (AR) gene and idiopathic male infertility is still unclear, ethnic background of the population studied may play an important role in this association. The objective of this study was to determine whether changes in the CAG repeat length are associated with spermatogenic defects in Turkish infertile men. Reproductive hormone concentrations and the CAG repeat length in exon 1 of the AR gene in 47 idiopathic infertile men and 32 fertile controls were analyzed. The mean serum luteinising hormone (LH) and follicle stimulating hormone (FSH) levels were significantly higher in the infertile group than those of the control group (p < 0.0001 for both comparisons), whereas the mean serum testosterone level in the infertile group did not differ significantly from that in the control group (p = 0.16). The mean CAG repeat length of the AR gene in the infertile group did not differ significantly from that in the control group (22.28 ± 0.37 vs 22.41 ± 0.54, respectively; p = 0.84). In addition, the frequency of having a CAG repeat number ( 24) was also comparable between the infertile patients and fertile controls (31.9% vs 40.6%, respectively; p = 0.21). In conclusion, reproductive hormones with elevated LH and FSH, and normal or low testosterone levels were suggestive of partial impairment of testicular function. However, no statistically significant relationship between the length of the CAG repeat and idiopathic impaired sperm production was observed in the Turkish population studied. These results support the findings of previously published European studies, but are contrary to the findings from Caucasian and North American population studies. Thus, ethnicity and genetic backgrounds seem to be important in this association, and studies from a variety of different ethnic and genetic backgrounds using

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Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility

Cited by 56 publications

References 20 publications

Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene

Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene

Semen quality is influenced by androgen receptor and aromatase gene synergism

No Association of the CAG Repeat Length in Exon 1 of the Androgen Receptor Gene with Idiopathic Infertility in Turkish Men: Implications and Literature Review

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