Is Increased Cag Repeat Length in the Androgen Receptor Gene a Risk Factor for Male Subfertility?

Golde, R. van; Houwelingen, Kjeld van; Kiemeney, Lambertus A.; Kremer, J.A.M.; Tuerlings, J.H.A.M.; Schalken, Jack A.; Meuleman, E.J.H.

doi:10.1097/00005392-200202000-00037

Cited by 18 publications

(23 citation statements)

References 25 publications

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“…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%

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: 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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“…18 Extremely long repeats of more than 40 CAG sequences leads to Kennedy's disease, which presents with neuromuscular symptoms, hypogonadism and impaired sperm production. 19 Even within the normal range, that is, between 15-30 repeats, there seems to be a negative correlation between the repeat number and androgen sensitivity, sperm production and fertility. [18][19][20][21] Average number of CAG repeats is inversely correlated with the incidence of prostate cancer in different ethnic groups: African-American men, who have a high incidence of prostate cancer, have shorter mean CAG sequences (mean ¼ 18-19) than Caucasians (mean ¼ 22) and Asians (mean ¼ 23) who have lower and the lowest PC incidences, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…19 Even within the normal range, that is, between 15-30 repeats, there seems to be a negative correlation between the repeat number and androgen sensitivity, sperm production and fertility. [18][19][20][21] Average number of CAG repeats is inversely correlated with the incidence of prostate cancer in different ethnic groups: African-American men, who have a high incidence of prostate cancer, have shorter mean CAG sequences (mean ¼ 18-19) than Caucasians (mean ¼ 22) and Asians (mean ¼ 23) who have lower and the lowest PC incidences, respectively. 22 Some analytical studies have also shown an increased risk of prostate cancer among males with low number of CAG repeats 23,24 although evidence is equivocal.…”

Section: Discussionmentioning

confidence: 99%

Reduced risk of prostate cancer in men who are childless as compared to those who have fathered a child: A population based case‐control study

Giwercman

Richiardi

Kaijser

et al. 2005

Intl Journal of Cancer

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Androgens are believed to play a major role in the etiology of prostate cancer, but studies of sex-hormone exposure in relation to risk for prostate cancer have been inconclusive. Male fertility may be an indicator of long-term androgen status. To study the role of testicular function in prostate cancer development, we have assessed number of biological children in relation to risk for this malignancy. We carried out a population-based case-control study with retrospective ascertainment of cases occurring in Sweden between 1958-98. In total, 48,850 cases of prostate cancer were identified through the nation-wide Cancer Registry. For each case, one control, matched by year of birth, was randomly selected from the Swedish population. Information on offspring was obtained from the Swedish Multi-Generation Registry. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between number of offspring and risk for subsequent prostate cancer. Being childless or having fathered one child only were associated with reduced risks for prostate cancer compared to having fathered 2 or more children (OR = 0.83; 95% CI = 0.81-0.86 and OR = 0.93; 95% CI = 0.90-0.96, respectively). There was no further change in risk associated with fathering of more than 2 children. The risk for prostate cancer is reduced among childless men. A dysfunctioning reproductive apparatus fueling to a lesser extent prostatic growth, could be a plausible mechanism of this association. ' 2005 Wiley-Liss, Inc.

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“…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). Interestingly, a study by Komori et al (1999) has suggested that reduction rather than expansion of the CAG repeat (< 16 repeats) is closely related to impaired sperm production in an infertile Japanese population.…”

Section: Discussionmentioning

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%

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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Is Increased Cag Repeat Length in the Androgen Receptor Gene a Risk Factor for Male Subfertility?

Abstract: Increased length of CAG repeats in the androgen receptor gene is not a risk factor for male subfertility.

Cited by 18 publications

References 25 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

Reduced risk of prostate cancer in men who are childless as compared to those who have fathered a child: A population based case‐control study

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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