Study of the effect of CAG polymorphism of the androgen receptor (AR) gene on spermatological parameters in Russian men

Полиморфизм CAG-повторов в экзоне 1 гена андрогенового рецептора (AR/HUMARA) ассоциирован с патозооспермией и нарушением мужской фертильности, однако его влияние на сперматогенез и показатели семенной жидкости недостаточно изучено. В статье представлены результаты исследования влияния количества CAG-повторов гена AR на показатели спермограммы у российских мужчин с бесплодием в браке, связанным с патозооспермией (n=451), и у мужчин с нормозооспермией - контрольная группа (n=131). Не выявлено зависимости концентрации и общего количества сперматозоидов в эякуляте, доли (%) прогрессивно подвижных (PR), морфологически нормальных и живых сперматозоидов от количества CAG-повторов гена андрогенового рецептора. У пациентов с тератозооспермией количество CAG-повторов статистически значимо выше, чем у мужчин без тератозооспермии (22,37±3,20 против 22,15±3,12; р=0,02). Polymorphism of CAG repeats in exon 1 of the androgen receptor gene (AR/HUMARA) is associated with pathozoospermia and male sub-/infertility, but its effect on spermatogenesis and seminal fluid parameters is under evaluated. The article presents the results of a study of CAG repeats in AR gene on semen parameters in Russian male patients from infertile couples with pathozoospermia (n = 451), and in normozoospermic men, a control group (n = 131). The analysis of the groups revealed no dependence of the concentration indices, the total amount and amount (%) of progressively motile («PR»), morphologically normal and live spermatozoa from the number of CAG repeats of the AR gene. Teratozoospermic patients have statistically significantly higher number of CAG repeats, than men without teratozoospermia (22.37 ± 3.20 versus 22.15 ± 3.12; p = 0.02).

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Cag Repeat Number in Androgen Receptor Gene and Male Infertility

Balkan Journal of Medical Genetics ◽

10.2478/v10034-007-0003-8 ◽

2007 ◽

Vol 10 (1) ◽

pp. 19-24 ◽

Cited By ~ 3

Author(s):

T Plaseski ◽

P Noveski ◽

C Dimitrovski ◽

B Kocevska ◽

G Efremov ◽

...

Keyword(s):

Androgen Receptor ◽

Male Infertility ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Cag Repeat ◽

Cag Repeats ◽

Control Group ◽

Repeat Number ◽

Number Of Patients ◽

Exon 1

Cag Repeat Number in Androgen Receptor Gene and Male InfertilityAndrogens are essential for male sexual development and for fertility. They exert their action through the androgen receptor (AR), a ligandactivated transcription factor. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that varies in number between 10 to 36 in the normal population. There is controversy over an association between high CAG repeat numbers in the AR gene and male infertility. We have evaluated the possible effect of long CAG repeats in the AR on infertility in men from the Republic of Macedonia (R. Macedonia). A group of 222 infertile/subfertile males with different sperm counts and a control group of 152 proven fathers were studied. The CAG repeat number was determined by fluorescent polymerase chain reaction (PCR) amplification of exon 1 of the AR gene analyzed by capillary electrophoresis. Mean CAG length did not differ significantly between males with azoospermia (22.0 ± 3.1), mild oligozoospermia (22.4 ± 2.6), severe oligozoospermia (23.0 ± 4.2), normozoospermia (21.8 ± 2.4), or known causes of infertility (22.1 ± 2.9) and fertile controls (22.3 ± 2.9). However, we found a significantly higher percentage of CAG repeats >26 (p = 0.022), >27 (p = 0.018) and >28 (p = 0.009) in males with mild oligozoospermia. These results indicate a possible association between CAG repeat length and mild oligozoospermia. Further studies on a larger number of patients with mild oligozoospermia are warranted to confirm this association.

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CAG polymorphism of the Androgen Receptor gene and semen parameters in pathozoospermic patients with and without Y chromosome microdeletions, and in normozoospermic men

Andrology and Genital Surgery ◽

10.17650/1726-9784-2021-22-2-66-77 ◽

2021 ◽

Vol 22 (2) ◽

pp. 66-77

Author(s):

L. P. Melikyan ◽

E. A. Bliznetz ◽

M. I. Shtaut ◽

A. O. Sedova ◽

T. M. Sorokina ◽

...

Keyword(s):

Androgen Receptor ◽

Y Chromosome ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Trinucleotide Repeats ◽

Cag Repeats ◽

Semen Parameters ◽

Control Group ◽

Y Chromosome Microdeletions ◽

Significant Difference

Introduction. The effect of polymorphic variants of the androgen receptor gene (AR) on spermatogenesis and semen parameters in men with different genotypes for other loci has not been sufficiently studied.The aim of this work was to study the effect of the (CAG)n polymorphism of the AR gene on semen parameters in men with impaired fertility, with and without partial deletions of the AZFс region from the Y chromosome.Materials and methods. The study included 988 unrelated Russian patients with pathozoospermia, including 591 patients without Y chromosome microdeletions and 397 patients with partial deletions of the AZFc region of the Y chromosome. The control group consisted of 131 normozoospermic men. All men who participated in the study underwent semen analysis and genetic testing. Genomic DNA was isolated from peripheral venous blood lymphocytes and ejaculate. The analysis of the polymorphism of (GAG)n repeat in exon 1 of the AR gene was performed using a polymerase chain reaction by the amplified fragment length polymorphism method.Results. Three groups were studied: patients with pathozoospermia with (n = 32) and without (n = 541) Y chromosome microdeletions, and normozoospermic men (control, n = 131). The median and quartiles of the number of CAG repeats in the groups were 22 and 20-25, respectively. According to the number of trinucleotide repeats of the AR gene, all patients were divided into subgroups: carriers of short ((GAG)n ≤18), medium ((GAG)n = 19-25) and long ((GAG)n ≥26) alleles. Medium alleles prevailed in all groups; in men without AZFc deletions and with microdeletions, their frequency was 79.3 and 81.4 %, respectively, in controls - 81.7 %.Conclusion. No correlation was found in examined cohort for semen parameters (sperm concentration and total number, number of live, progressively motile and morphologically normal spermatozoa) from the number of trinucleotide repeats. However, a statistically significant difference (p ≤0.045; FDR correction) was found in concentration and total number, number of live, progressively motile and morphologically normal spermatozoa when comparing men with nomrozoospermia (control) with patients with pathozoospermia with and without partial AZFc deletions in subgroups of carriers of short, medium and long alleles.

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Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism

Acta Endocrinologica ◽

10.1530/eje.1.01860 ◽

2005 ◽

Vol 152 (3) ◽

pp. 419-425 ◽

Cited By ~ 42

Author(s):

Alberto Ferlin ◽

Andrea Garolla ◽

Andrea Bettella ◽

Lucia Bartoloni ◽

Cinzia Vinanzi ◽

...

Keyword(s):

Androgen Receptor ◽

Receptor Gene ◽

Causative Factor ◽

Androgen Receptor Gene ◽

Cag Repeats ◽

Exon 1 ◽

History Of ◽

Receptor Gene Polymorphisms ◽

Congenital Birth Defect

Objective: Cryptorchidism is the most common congenital birth defect in male children, and accumulating evidence suggests that genetic abnormalities may be associated with it. The androgen receptor has two polymorphic sites in exon 1, with different numbers of CAG and GGC repeats, resulting in variable lengths of polyglutamine and polyglycine stretches. Longer CAG repeats result in a reduced androgen receptor transcriptional activity, but the role of the GGC triplets is less clear. In this study we analysed CAG and GGC repeat lengths in men with a history of cryptorchidism, associated or not with impairment of sperm production, in comparison with normal fertile subjects. Methods: We analysed CAG and GGC repeat lengths in a group of 105 ex-cryptorchid men in comparison with 115 fertile non-cryptorchid men. Results: No difference was found between patients and controls in the mean and median values, and in distribution of CAG and GGC, when considered separately. However, the analysis of the joint distribution of CAG and GGC showed that some combinations are significantly more frequent in men with bilateral cryptorchidism (who frequently presented severe testiculopathies), in a manner similar to that found in idiopathic infertile subjects. Conclusions: Although further studies are needed to elucidate the possible role of specific CAG/GGC combinations as a causative factor, these data suggest a possible association between androgen receptor gene polymorphisms and cryptorchidism.

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Polymorphism of CAG Repeats in Exon 1 of the Androgen Receptor Gene in Russian Men with Various Forms of Pathozoospermia

Russian Journal of Genetics ◽

10.1134/s1022795420080104 ◽

2020 ◽

Vol 56 (8) ◽

pp. 1000-1005

Author(s):

L. P. Melikyan ◽

E. A. Bliznetz ◽

A. V. Polyakov ◽

O. L. Mironovich ◽

I. A. Kuznetsova ◽

...

Keyword(s):

Androgen Receptor ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Cag Repeats ◽

Exon 1

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Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study

International Journal of Endocrinology ◽

10.1155/2016/5083569 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Giacomo Tirabassi ◽

Giovanni Corona ◽

Sara Falzetti ◽

Nicola delli Muti ◽

Mario Maggi ◽

...

Keyword(s):

Androgen Receptor ◽

Sexual Function ◽

Erectile Function ◽

Receptor Gene ◽

Cross Sectional Study ◽

Androgen Receptor Gene ◽

Cag Repeats ◽

Cross Sectional ◽

Cag Polymorphism ◽

Sexual Assessment

Background. No study has assessed the possible involvement of GGC androgen receptor (AR) polymorphism in sexual function. Our aim is to evaluate the association between CAG and GGC AR polymorphisms in this function.Methods. We retrospectively examined eighty-five outpatients. Clinical, biochemical, and genetic parameters were considered. Sexual assessment was performed using the International Index of Erectile Function (IIEF) which evaluates erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS).Results. In the whole sample, CAG repeats were inversely correlated with EF, OF, and total IIEF-15 score, whereas GGC tracts did not show any significant correlation with sexual function. CAG relationship with IIEF items retained significance only in the eugonadal but not in the hypogonadal cohort. On the other hand, GGC tracts were not found to be significantly correlated with IIEF variables in either eugonadal or hypogonadal subjects. In eugonadal subjects, logistic regression pointed out that a higher number of CAG triplets were associated with lower values of EF, OF, SD, OS, and total IIEF independently from other confounders.Conclusions. GGC polymorphism seems not to exert any influence on sexual function, whereas CAG polymorphism appears to affect sexual parameters only in eugonadal subjects.

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