Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility

Mifsud, Amparo; Sim, Chris K.S; Boettger‐Tong, Holly; Moreira, Sergio G.; Lamb, Dolores J.; Lipshultz, Larry I.; Yong, Eu Leong

doi:10.1016/s0015-0282(00)01693-9

Cited by 123 publications

(117 citation statements)

References 23 publications

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“…Data from some studies have established that AR missense substitutions contribute about 2 % and CAG repeat expansion (>28 repeats) may contribute up to 35 % of male infertility cases [82]. A preliminary research indicated that the mean AR gene CAG repeat length was significantly larger in azoospermic subjects than in control fertile men [84]. Mutations in TAD range from point mutations, insertions or deletions, or altered CAG repeats of AR gene.…”

Section: The Androgen Receptor (Ar) Gene Mutationsmentioning

confidence: 99%

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

Tahmasbpour

Balasubramanian

Agarwal

2014

J Assist Reprod Genet

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Background The assisted reproductive techniques aimed to assist infertile couples have their own offspring carry significant risks of passing on molecular defects to next generations. Results Novel breakthroughs in gene and protein interactions have been achieved in the field of male infertility using genome-wide proteomics and transcriptomics technologies. Conclusion Male Infertility is a complex and multifactorial disorder.Significance This review provides a comprehensive, up-todate evaluation of the multifactorial factors involved in male infertility. These factors need to be first assessed and understood before we can successfully treat male infertility.

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Section: The Androgen Receptor (Ar) Gene Mutationsmentioning

confidence: 99%

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

Tahmasbpour

Balasubramanian

Agarwal

2014

J Assist Reprod Genet

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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: 89%

“…Also within the subgroups of infertile males presenting with varying degrees of impaired sperm production (azoospermia, severe oligozoospermia, oligozoospermia and poor motility/morphology only group) we found no statistically significant association between the size of their respective CAG repeats or polyglutamine tracts and the severity of impaired sperm production (Table 2). Tut et al (1997) suggested that an enlargement of the CAG tract repeats ( 28) in infertile males is associated with a 4-fold increased risk of infertility, whereas Mifsud et al (2001) reported the odds ratio for azoospermia as 7-fold higher for patients with 26 CAG repeats than in those with < 26 CAG repeats. These studies suggested that the more severe the spermatogenic defect the higher the CAG repeat number should be.…”

Section: Discussionmentioning

confidence: 99%

“…The genomic DNA samples of all the subjects were blind-coded and the CAG repeat length of the AR gene was assessed by means of a PCR with primers specific for the repeat segment (sense primer: 5´-TCCAGAATCT GTTCCAGAGCGTGC, and antisense primer: 5´-GCTGTGAAGGTTGCTGTTCCTC; Mifsud et al 2001; Fig. 1).…”

Section: Polymerase Chain Reaction (Pcr) Of the Ar Gene And Trinucleomentioning

confidence: 99%

“…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%

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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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Analysis of the polymorphic CAG repeat length in the androgen receptor gene in patients with testicular germ cell cancer

Meyts¹,

Leffers²,

Daugaard³

et al. 2002

Intl Journal of Cancer

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Changes in the length of a polymorphic trinucleotide (CAG) repeat in the androgen receptor (AR) gene, which may lead to altered transactivation of the AR gene, have been implicated to play a role in the pathogenesis of several forms of endocrine cancer and certain reproductive disorders. Subjects with reproductive disorders that are associated with a relative deficiency of androgen function carry an increased risk for testicular cancer, therefore we have examined the (CAG)n in the AR gene in DNA isolated from peripheral blood cells of 102 patients diagnosed with testicular germ cell neoplasia and compared them with a control group of 110 healthy men with proven fertility. All patients and control subjects underwent comprehensive andrological examination that included reproductive hormone profiles and the analysis of the (CAG)n in the AR gene that was done by means of PCR and DNA sequencing. There was no difference in the distribution of (CAG)n between the subjects and controls, no association of (CAG)n and the tumor type and no association with severity of the disease. We conclude that the high risk of testicular germ cell cancer in the Danish population is not associated with the (CAG)n polymorphism in the AR gene.

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Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility

Cited by 123 publications

References 23 publications

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

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

Analysis of the polymorphic CAG repeat length in the androgen receptor gene in patients with testicular germ cell cancer

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