Genetic Association Between Androgen Receptor Gene CAG Repeat Length Polymorphism and Male Infertility

Pan, Bihui; Li, Rui; Yao, Chen; Tang, Qiuqin; Wu, Wei; Chen, Liping; Lu, Chuncheng; Pan, Feng; Ding, Hongjuan; Xia, Yankai; Hu, Lingqing; Chen, Daozhen; Sha, Jiahao; Wang, Xinru

doi:10.1097/md.0000000000002878

“…However, several studies from North America, Singapore and Australia were able to show a clear significant correlation between CAG repeat length and infertility such as patients with increased risk of spermatogenesis impairment had longer AR‐CAG repeats (Dowsing et al., ; Patrizio, Leonard, Chen, Hernandez‐Ayup, & Trounson, ; Tut, Ghadessy, Trifiro, Pinsky, & Yong, ). Shorter CAG repeats have also been shown to be associated with oligozoospermia (Komori et al., ) albeit with a lower risk towards male infertility when compared to the effect of longer CAG repeats (Pan et al., ; Xiao et al., ). The discrepancy between the aforementioned studies could be explained by several factors including ethnic differences and genetic backgrounds of the various populations studied, differences in inclusion criteria of patients, and sample size among others.…”

Section: Discussionmentioning

confidence: 99%

“…The association between CAG repeat length expansion and male infertility shows conflicting results in studies involving different ethnic groups (Davis‐Dao et al, ; Pan et al, ). In this study, we investigated the molecular role of Y chromosome microdeletions and the AR‐CAG expansion in a group of Jordanian azoospermic patients.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of CAG repeat length of the androgen receptor gene and Y chromosome microdeletions among Jordanian azoospermic infertile males

Batiha

¹

,

Haifawi

²

,

Al-Smadi

³

et al. 2018

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Assisted reproductive technology is a common procedure which helps millions of couples who suffer fertility problems worldwide every year. Screening for genetic abnormalities prior to such procedure is very important to prevent the transmission of harmful genetic mutations to future generations. Microdeletions within the azoospermia factor (AZF) region of the Y chromosome and the expansion of the CAG trinucleotides in the androgen receptor (AR) gene are among the susceptible causes of male infertility in different ethnic groups. Such association has never been studied in Jordan. In this study, we compared CAG repeat length between azoospermic infertile and normospermic fertile Jordanian males and we also screened the frequency of Y chromosome microdeletions in the same cohort. The study included 142 nonobstructive azoospermic cases and 145 normospermic controls. Results have shown that the median CAG repeat length in the azoospermic group is 19 ± 2 compared to 19 ± 1.5 (p = .6262) in the control group. Deletions within the Y chromosome AZF region were detected in 7 of 142 cases (4.93%) and no deletions were seen in the control group. The results of this study confirm the importance of the AZF region in normal spermatogenesis, whereas it shows no link between the length of CAG repeats in the AR gene and male azoospermia in Jordanian group examined.

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“…Two polymorphisms, the CAG and GGN polymorphisms, located in exon 1 of the AR gene, code for polyglutamine and polyglycine stretches respectively. Longer lengths of the CAG repeat are associated with decreased transcriptional activity of the AR protein in vitro, suggesting that longer polyglutamine tracts may be related to male infertility (104,105,106). Thus, the CAG repeat length has been extensively studied for their role in male infertility.…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

Aberrations on the X-chromosome as cause of male infertility

Tüttelmann¹

2016

EJEA

1

0

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Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo-or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the maleassociated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years.

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“…Thus, the CAG repeat length has been extensively studied for their role in male infertility. However, overall statistically significant, but very small and thus clinically irrelevant differences have been determined between infertile men and controls (105,107,108,109). Variations of the GGN polymorphism are frequently found in the general male population and are not associated with male infertility (109,110,111,112,113).…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

“…Longer lengths of the CAG repeat are associated with decreased transcriptional activity of the AR protein in vitro, suggesting that longer polyglutamine tracts may be related to male infertility (104,105,106). Thus, the CAG repeat length has been extensively studied for their role in male infertility.…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility

Röpke

¹

,

Tüttelmann

²

2017

European Journal of Endocrinology

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Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo-or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the maleassociated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years.

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Genetic Association Between Androgen Receptor Gene CAG Repeat Length Polymorphism and Male Infertility

Abstract: Supplemental Digital Content is available in the text

Cited by 32 publications

References 59 publications

Molecular analysis of CAG repeat length of the androgen receptor gene and Y chromosome microdeletions among Jordanian azoospermic infertile males

Molecular analysis of CAG repeat length of the androgen receptor gene and Y chromosome microdeletions among Jordanian azoospermic infertile males

Aberrations on the X-chromosome as cause of male infertility

MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility

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