雄激素受体基因CAG多态性对男性激素避孕有效性影响的研究

目的:分析应用肌注十一酸睾酮酯(TU)进行激素避孕的男性志愿者中起反应者与不起反应者雄激素受体(AR)基因(CAG)n微卫星多态性,并探讨该多态性对激素避孕效果的影响。方法:29例TU不起反应者和34例起反应者分别作为试验组和对照组,应用PCR和DNA测序技术对两组外周血标本进行CAG重复数测定,分析该微卫星多态性对激素避孕效果的影响。结果:试验组和对照组CAG重复数的均数分别为23.62和22.97,均数比较差异无显著性(P>0.05)。短组CAG(n≤22)在试验组和对照组的分布分别为51.7%、50.0%;长组CAG(n>22)在试验组和对照组分布分别为48.3%、50.0%,长短组分布相同。CAG重复数与精子密度之间未见相关性。在FSH浓度>0.2IU/L组中,CAG重复数>22的受试者达到无精子症的机会是其他受试者的1.5倍。结论:受试者AR基因(CAG)n重复数呈多态性,但不反应组与反应组之间不具有显著性差异,AR基因CAG重复数或其他因素与男性激素避孕效果之间的关系有待进一步探讨。     

雄激素受体基因CAG多态性对男性激素避孕有效性影响的研究

目的：分析应用肌注十一酸睾酮酯（TU）进行激素避孕的男性志愿者中起反应者与不起反应者雄激素受体（AR）基因（CAG）n微卫星多态性，并探讨该多态性对激素避孕效果的影响。方法：29例TU不起反应者和34例起反应者分别作为试验组和对照组，应用PCR和DNA测序技术对两组外周血标本进行CAG重复数测定，分析该微卫星多态性对激素避孕效果的影响。结果：试验组和对照组CAG重复数的均数分别为23．62和22．97，均数比较差异无显著性（P〉0．05）。短组CAG（n≤22）在试验组和对照组的分布分别为51．7％、50．0％；长组CAG（n〉22）在试验组和对照组分布分别为48．3％、50．0％，长短组分布相同。CAG重复数与精子密度之间未见相关性。在FSH浓度〉0．2IU／L组中，CAG重复数〉22的受试者达到无精子症的机会是其他受试者的1．5倍。结论：受试者AR基因（CAG）n重复数呈多态性，但不反应组与反应组之间不具有显著性差异，AR基因CAG重复数或其他因素与男性激素避孕效果之间的关系有待进一步探讨。     

无精或严重少弱精症患者雄激素受体基因(CAG)n多态性的研究

作为遗传标记的雄激素受体（AR）基因多态性（CAG）n与男性精子生成障碍及不育有关。我们调查了本中心部分无精或严重少弱精症患者（CAG）n序列的多态性，探讨该基因重复多态性与男性精子生成障碍的关系，现报告如下。     

雄激素受体基因CAG重复多态性与男性不育关系的Meta分析

目的:采用Meta分析系统评价雄激素受体(AR)基因CAG串联重复多态性与男性不育的关系。方法:检索Medline、CBM等数据库中有关AR基因CAG重复数与男性不育相关性的病例对照研究,并用RevMan4.2软件进行统计分析。结果:共纳入32篇符合条件的文献,累计特发性不育病例3153例、对照2314例。数据合并结果显示,男性不育、无精子症及中度少精子症者其CAG重复数均数均显著高于对照人群(P<0.01),三者与对照间CAG重复数均数的标准均数差分别为0.27,95%CI:0.17～0.37;0.29,95%CI:0.08～0.50;0.27,95%CI:0.13～0.41。而且,敏感性分析结果也与以上研究结果一致。结论:AR基因CAG重复多态性其重复数增多与精子发生障碍的风险相关。     

特发性无精子症和少精子症患者谷胱甘肽S-转移酶T1基因的遗传多态性

目的:探讨谷胱甘肽S-转移酶T1基因多态性(GSTT1)与特发性无精子症和少精子症的关系。方法:按WHO手册标准,采用WLJY-9000伟力彩色精子质量检测系统对研究对象进行精液分析,根据精液检测结果将研究对象分成特发性无精子症组(n=34)、少精子症组(n=40)和正常对照组(n=53),各组研究对象年龄、吸烟史、饮酒史无统计学差异。基因组DNA来自研究对象提供的外周血有核细胞,采用聚合酶链反应(PCR)方法对研究对象GSTT1基因进行分型。结果:特发性无精子症组、少精子症组GSTT1缺失型基因频率分别为76.5%和72.5%,明显高于正常对照组(49.1%),差异有统计学意义(无精子症组vs正常对照组,OR=3.13,95%CI为1.20～8.16,P=0.020;少精子症组vs正常对照组,OR=2.53,95%CI为1.06～6.11,P=0.038)。结论:GSTT1基因多态性与特发性无精子症、少精子症有相关性;GSTT1缺失基因型是特发性无精子症和少精子症发病的危险因素。     

无精子症和严重少精子症患者Y染色体微缺失和基因缺失研究

目的研究中国特发性无精子症和少精子症患者Y染色体无精子症因子(AZF)区缺失和其中RBMY1A1、DAZ基因缺失。方法选取AZFa、b和c区6个序列标签位点(STS)对56例少精子症和33例无精子症患者进行外周血Y染色体微缺失分析,对缺失样本进行RBMY1A1和DAZ基因缺失分析。结果共确认6例患者发生Y染色体微缺失和基因缺失、占7%(6/89);其中5例AZFc/DAZ基因缺失,1例AZFb+c/RBMY1A1和DAZ基因缺失。结论AZF部分区域缺失的患者同时伴有与精子生成具有重要作用的基因缺失,并可能由此导致精子生成障碍。     

雄激素受体基因CAG多态性与迟发性性腺功能减退症的相关性研究

目的:研究雄激素受体基因(AR)重复序列(CAG)n多态性与迟发性性腺功能减退症(LOH)的关系,探讨LOH的发病机制。方法:共调查1 000例40～70岁中老年男性,其中19例迟发性性腺功能减退症患者,随机抽取127例正常健康中老年男性,测定甘油三酯(TG)、空腹血糖(FBG)、血清总睾酮(TT)、游离睾酮(fT),测量身高、体重、腰围(WC)、血压,并采用DNA测序方法进行AR基因外显子1氨基端转录调节区(CAG)n重复序列长度测定,比较两组各指标之间的差异。结果:(CAG)n重复次数为15～32(23.05±2.95)。正常健康中老年男性的体重指数(BMI)、FBG较LOH患者显著下降(P<0.01),而TG、TT及fT较LOH患者显著升高(P<0.01)。正常健康中老年男性AR基因(CAG)n重复数为22.54±3.06;LOH患者AR基因(CAG)n重复数为23.23±2.24;LOH患者(CAG)n重复数略高于正常健康人群,但两者比较无统计学意义(P=0.946)。(CAG)n重复长度显示:长组(n≥22)AR基因(CAG)n在LOH组和正常健康中老年男性组的频率分别为73.68%和48.82%(P<0.05)。相关分析显示:TT、fT与(CAG)n重复序列无明显相关性(r=0.04和r=0.025,P>0.05)。结论:LOH男性AR基因(CAG)n重复序列呈现多态性,长(CAG)n重复多态可能是LOH发病的遗传因素,但仍需进一步扩大样本量证实。     

前列腺癌与雄激素受体基因(CAG)n重复多态性的关系

目的　探讨前列腺癌 (PC)与雄激素受体 (AR)基因 (CAG)n重复多态性的关系。　方法　应用DNA双链循环测序方法对 34例PC组织与癌旁正常组织、2例PC患者外周血白细胞内的AR基因 (CAG)n重复数进行测定。　结果　同一PC患者的癌组织与癌旁正常组织 (CAG)n重复数相同 ;36例患者癌组织AR基因 (CAG)n呈重复多态性 ,平均 2 0 .0 6 ,显著低于正常组织 ,差别有显著性意义 (P <0 .0 5 ) ;不同分化程度的癌组织 (CAG)n重复数差别无显著性意义 (P >0 .0 5 )。　结论　AR基因 (CAG)n重复数改变的体细胞突变在PC癌细胞中罕见 ,该重复数的减少可能与PC发病相关     

男性FASL-844基因多态性与特发性无精子症及严重少精子症发病风险的研究

目的:研究FASL-844位点基因多态性在中国南方汉族男性人群中的分布,探讨其与特发性无精子症及严重少精子症发病风险的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析184例特发性无精子症及严重少精子症患者与236例正常生育男性FASL-844位点的基因型及等位基因频率,分析该基因多态性与特发性无精子症及严重少精子症之间的关系。结果:不育组与正常生育组FASL-844CT和TT基因型分布差异有显著性(P=0.024;P=0.008)。携带FASL-844TT基因型个体罹患特发性无精子症或严重少精子症的风险是CC基因型个体的2.76倍(95%CI:1.20~6.35);将携带CC和CT基因型的个体合并,携带TT基因型的个体罹患特发性无精子症或严重少精子症的风险是(CC+CT)基因型个体的2.90倍(95%CI:1.28~6.58)。结论:FASL-844基因多态性可能是中国南方汉族男性特发性无精子症及严重少精子症的遗传易感因素之一。     

无精或严重少弱精症与雄激素受体基因重复多态性的关系

目的探讨无精或严重少弱精症患者与雄激素受体基因(CAG)n重复多态性的关系。方法应用DNA双链循环测序方法,对32例无精或严重少弱精症患者(不育组)、15例正常生育男性(对照组),进行外周血雄激素受体基因(CAG)n重复数的测定。结果不育组32例患者(CAG)n重复数为17~25,平均21.08±2.1;对照组15例为11~27,平均21.2±2.3。两者比较差异无统计学意义。结论无精或严重少弱精症患者与雄激素受体基因(CAG)n重复数的没有关系。     

Association of oestrogen receptor alpha polymorphisms and androgen receptor CAG trinucleotide repeats with male infertility: a study in 109 Greek infertile men

This study was performed to examine the contribution of genetic polymorphism of oestrogen and androgen receptor (AR) genes in male infertility. We have studied in total 173 Greek men, 109 infertile patients and 64 controls (group A). Patients were divided in to three subgroups: group B (n=29) with idiopathic moderate oligospermia, group C (n=42) with azoospermia or idiopathic severe oligospermia and group D (n=38) with azoospermia or oligospermia of various known aetiologies. All patients and controls were genotyped for two polymorphisms of the oestrogen receptor alpha (ERalpha) gene and also for the (CAG)n repeat length polymorphism of the X-linked androgen receptor (AR)gene. The control group had statistically significant difference from group C regarding the XbaI polymorphism of ERalpha gene. Despite the fact that we did not observe any statistically significant differences in the mean and range of the CAG repeat number, the frequency of the higher repeats of the nucleotide repeat sequence (CAG)n of the AR gene was 2-4 times higher in groups B and C compared with the control group A. Our results indicate that both ERalpha and AR gene play significant role in male fertility. It is possible that a synergy may exist between unfavourable genotypes of these two genes in male infertility.     

CAG repeat length in the androgen receptor gene is enhanced in patients with idiopathic azoospermia

Objectives. To determine whether the number of CAG repeats in the androgen receptor gene is enhanced in patients with idiopathic azoospermia.Methods. Using the polymerase chain reaction, the number of CAG repeats was assayed in 41 patients with idiopathic azoospermia and in 48 normozoospermic fertile men.Results. In the control group, the CAG repeat length ranged from 17 to 30 (mean 23.9 ± 2.9); in the azoospermic group, the CAG repeat length ranged from 20 to 34 (mean 26.5 ± 3.5). The difference between the two groups was statistically significant (P = 0.0013). None of the men in the control group had a CAG repeat length greater than 31; four of the azoospermic men had 34 CAG repeats.Conclusions. Results suggest that an increase in the number of CAG repeats in the androgen receptor gene to 31 or greater may be associated with the etiology of at least some cases of idiopathic azoospermia.     

Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men

The genetic basis of male infertility remains unclear in the majority of cases. Recent studies have indicated an association between microdeletions of the azoospermia factor a (AZFa)-AZFc regions of Yq and severe oligospermia or azoospermia. Increased (CAG)n repeat lengths in the androgen receptor (AR) gene have also been reported in infertile men. Therefore, in order to assess the prevalence of these genetic defects to male infertility, 183 men with non-obstructive azoospermia (n = 70), obstructive azoospermia (n = 33), severe oligospermia (n = 80) and 59 fertile men were examined cytogenetically and at molecular level for Yq deletions, microdeletions, and AR-CAG repeat lengths along with hormonal profiles [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T)]. We used high resolution cytogenetics to detect chromosome deletions and multiplex polymerase chain reaction (PCR) involving 27 sequence-tagged site (STS) markers on Yq to determine the rate and extent of Yq microdeletions. PCR amplification with primers flanking exon 1 of AR gene was used to determine the AR-(CAG)n repeat lengths. Hormonal profiles (LH, FSH and T levels) were also analysed in infertile and fertile men. Testicular biopsies showed Sertoli cell only (SCO) morphology, maturation arrests (MA) and hypospermatogenesis. No chromosome aberrations were found in infertile men but there was a significant increase (p < 0.001) in the association of acrocentric chromosomes including the Y chromosome. Yq microdeletions were found in 16 non-obstructive azoospermic men (16 of 70; 22%) and seven severe oligospermic individuals (seven of 80; 8.7%) and most of them had deletions in the sY240 locus. No Yq microdeletions were detected in patients with obstructive azoospermia. No statistically significant difference in the mean length of CAG repeats in AR gene was observed between infertile and fertile men (22.2 +/- 1.5 and 21.5 +/- 1.4 respectively). No significant increase or decrease in levels of LH, FSH and T was observed in infertile and fertile men. In some infertile men, significantly elevated levels of FSH alone or in combination with LH were found to be indicative of failure of spermatogenesis and/or suggestive of testicular failure. Y-chromosome microdeletions contribute to infertility in some patients but no relationship could be established with the (CAG)n repeat lengths in exon 1 of the AR gene in infertile Indian men.     

CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations

CAG repeat expansion in exon 1 of the androgen receptor (AR) gene has been reported to be associated with male infertility in some but not all populations. Until now, studies have not been carried out to examine this among Indian populations. For the first time, we have analyzed the CAG repeat motif in the AR gene in 280 men with azoospermia and in 201 men with normal fertility. The mean number of CAG repeats in the AR gene of men with azoospermia was 21.7 +/- 0.18, with a high incidence of repeat number 22. Among fertile-control men, the mean number of CAG repeats was 22.4 +/- 0.19, with a predominance of repeat number 23. The highest number of CAG repeats (32) was found with low frequency in both fertile and azoospermic groups. Comparison of fertile men and those with azoospermia on the basis of CAG repeats revealed that the number of CAG repeats in both groups were similar, as revealed with a paired t test (t = 0.04; P =.967). Expansion of the CAG repeat in the AR gene is therefore not associated with male infertility in Indian populations. This suggests that what is true for one population may not be true for other populations.     

An increased CAG repeat length in the androgen receptor gene in azoospermic ICSI candidates

The androgen receptor gene has a polymorphic trinucleotide repeat that encodes a polyglutamine tract in its N-terminal transactivation domain. We started this study in order to find out whether a correlation existed between the length of this polymorphic tract and the presence of azoospermia in candidates for intracytoplasmic sperm injection (ICSI). The CAG repeat length in exon 1 of the androgen receptor (AR) gene was directly sequenced in 102 patients with azoospermia and in 96 fertile controls. Hormone levels were also measured in patients with azoospermia. The mean AR gene CAG repeat length was significantly larger in azoospermic subjects than it was in control fertile men (23.25 +/- 2.7 versus 22.42 +/- 2.8; P =.033). A receiver operating characteristic analysis evidenced a cutoff point at 22/23 CAG repeats at which the probability of being azoospermic increased 2.2 times. Subsequent logistic regression analysis of the data showed that the odds for azoospermia increased with the number of CAG repeats. Men with more than 26 CAG repeats have a 4.09 greater risk of being azoospermic. Therefore, in our candidates for ICSI, a direct correlation exists between the CAG repeat length in the exon 1 of the AR gene and the risk of being azoospermic.     

CAG repeat length analysis and mutation screening of the androgen receptor gene in Japanese men with idiopathic azoospermia.

Because androgens are required for normal spermatogenesis, we are investigating abnormalities in the androgen receptor as a possible cause of impaired spermatogenesis in patients with idiopathic male infertility. The CAG repeat length in exon 1 and mutations of the androgen receptor gene were studied in 30 men with idiopathic azoospermia and in 51 fertile men. In men with azoospermia, plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were measured and testicular biopsies were performed. The CAG repeat length ranged from 19 to 30 (mean 23.4 +/- 2.9) and from 17 to 28 (mean 23.7 +/- 3.2) in men with azoospermia and in controls, respectively. There was no significant difference between the 2 groups. In men with azoospermia, the Johnsen testicular biopsy score negatively correlated with plasma FSH (P < .01). However, the Johnsen testicular biopsy score did not correlate with plasma LH and testosterone levels. The CAG repeat length did not correlate with the Johnsen testicular biopsy score, or with plasma concentrations of LH, FSH, and testosterone. No abnormalities in the androgen receptor gene were detected. These facts suggest that the CAG repeat length and alterations in the androgen receptor gene are not associated with the etiology of idiopathic azoospermia.     

Evidence for association of sex hormone-binding globulin and androgen receptor genes with semen quality

The roles of androgen receptor AR(CAG)n gene polymorphisms and sex hormone-binding globulin SHBG(TAAAA)n gene polymorphisms on semen quality were studied. One hundred fourteen men were included in the study: 85 with normal sperm count and 29 oligospermic. The genotype analysis, on DNA extracted from spermatozoa, revealed five SHBG(TAAAA)n alleles with 6–10 repeats and 18 AR(CAG)n alleles with 12–32 repeats. The SHBG allelic distribution showed that in men with normal sperm count and motility, those with short SHBG alleles had higher sperm concentration than men with long SHBG alleles ( P  = 0.039). As concerns AR(CAG)n polymorphisms, men with short AR alleles had lower sperm motility compared to those with long AR alleles ( P  < 0.001) in both total study population and normal sperm count men. The synergistic effect analysis of the two polymorphisms revealed an association between sperm motility ( P  = 0.036), because of the effect of AR(CAG)n polymorphism on sperm motility. In conclusion, long AR alleles were found to be associated with higher sperm motility, while short SHBG alleles were associated with higher sperm concentration, supporting the significance of these genes in spermatogenesis and semen quality.