Polymorphism in DNMT1 may modify the susceptibility to oligospermia.

As an important methyltransferase, DNMT1 plays a key role in DNA methylation that is essential for normal spermatogenesis, which suggests that it may be involved in male infertility with spermatogenesis impairment. To explore the relationship between DNMT1 and spermatogenesis impairment, polymorphic distributions of single-nucleotide polymorphisms (SNP) rs16999593, rs2228612 and rs2228611 in DNMT1 were investigated in 342 infertile patients with idiopathic azoospermia or oligospermia and 232 fertile controls in a Chinese population. As a result, no significant differences in allele and genotype frequencies of the three SNP between total patients and controls were observed. However, after stratifying the patients, significant differences in allele and genotype frequencies were detected between oligospermia subgroup and control group. The frequencies of rs16999593 allele A (83.6% versus 77.6%, P=0.033) and genotype AA (69.2% versus 59.0%, P=0.037) and SNP rs2228611 genotype AA (18.4% versus 9.9%, P=0.016) in patients with oligospermia were significantly higher than those in control group. These findings suggest that the polymorphism in DNMT1 might be associated with oligospermia and could modify the susceptibility of oligospermia.

Relationship of SNP of H2BFWT gene to male infertility in a Chinese population with idiopathic spermatogenesis impairment.

The H2B family, member W, testis specific (H2BFWT) gene encodes a testis specific histone that plays a crucial role in reorganization and remodeling of chromatin and epigenetic regulation during spermatogenesis, suggesting that the gene may be involved in spermatogenesis impairment. To test the speculation, the allele and haplotype frequencies of two single-nucleotide polymorphism loci in this gene, -9C>T and 368A>G, were investigated in 409 infertile patients with idiopathic azoospermia or oligozoospermia and 209 fertile men as controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. As the results, the frequencies of -9T (52.8% vs. 41.6%, p = 0.009) and 368G (43.0% vs. 32.5%, p = 0.012) were significantly higher in patients than those in controls; after stratifying patients, the significant higher frequencies were still detected in allele -9T for azoospermia (57.4% vs. 41.6%, p = 0.001) and allele 368G for oligozoospermia (45.4% vs. 32.5%, p = 0.007). The haplotype CA was significantly decreased (22.8% vs. 33.0%, p = 0.006) whereas TG was significantly increased (18.3% vs. 7.2%, p < 0.001) in infertile patients compared with controls. These results indicated that the polymorphism -9C>T and 368A>G in H2BFWT gene are associated with male infertility with idiopathic azoospermia or oligozoospermia, suggesting that H2BFWT gene might be contribute to susceptibility to spermatogenesis impairment in Chinese population.

Association between single-nucleotide polymorphisms of DNMT3L and infertility with azoospermia in Chinese men.

The gene for DNA methyltransferase 3-like protein (DNMT3L) is essential for normal spermatogenesis and may be involved with spermatogenetic impairment and male infertility. To explore the possible association between the DNMT3L gene and male infertility, this study investigated allele, genotype and haplotype frequencies of three single nucleotide polymorphism (SNP) loci, rs2070565, rs2276248 and rs7354779, of DNMT3L in 233 infertile patients with azoospermia and 249 fertile controls from a population of Chinese men using polymerase chain reaction/restriction fragment length polymorphism. Results showed that the frequencies of allele A (20.6% versus 14.9%; P = 0.022) and the allele A carrier (GA + AA; 37.8% versus 28.1%; P = 0.027) in azoospermic patients were significantly higher than those in controls at the rs2070565 locus. The haplotype AAA frequency was significantly higher (18.1% versus 12.4%; P = 0.02) while the haplotype GAA frequency was significantly lower (53.2% versus 62.1%; P = 0.007) in infertile patients compared with fertile controls. These results indicated that SNP rs2070565, as well as haplotypes AAA and GAA, may be associated with male infertility and suggest that DNMT3L may contribute to azoospermia susceptibility in humans.

[Single nucleotide polymorphisms of the genes related with spermatogenesis impairment].

Male infertility is a complex disease affecting the reproduction of childbearing couples, for which genetic polymorphism of spermatogenesis genes is an important genetic pathogenic factor. Lots of genes closely related with spermatogenesis have been successfully identified through the gene knockout technology. Spermatogenesis impairment related genes include those associated with expression enzymes, receptors, cell apoptosis, transcription regulation, and so on. The genetic susceptibility of these genes, infection, and environment jointly contribute to non-obstructive azoospermia and oligozoospermia in males. The analysis of the single nucleotide polymorphism (SNP) of spermatogenesis impairment related genes helps explain the possible mechanism of pathogenesis at the molecular level, and provides theoretical evidence for the clinical diagnosis and treatment of male infertility. The article focuses on the correlation of the SNPs of spermatogenesis impairment related genes with azoospermia and oligozoospermia.

Association of single nucleotide polymorphisms of PATZ1 gene with azoospermia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the relationship between the polymorphisms of single nucleotide polymorphisms(SNPs) in rs2240424, rs2057951, rs2240427 and rs714909 loci in the PATZ1 gene and azoospermia.</p><p><b>METHODS</b>The allele and genotype frequencies of the four SNPs were investigated in 180 patients with azoospermia and 190 normal men as controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The allele and genotype frequencies of the four SNPs were investigated in 180 patients with azoospermia and 190 normal men as controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis.</p><p><b>RESULTS</b>The frequencies of allele C (35.0% vs. 27.6%, P=0.031) and individuals with allele C (TC+CC) (57.8% vs. 46.3%, P=0.027) at the rs2057951 locus in azoospermic patients were significantly higher than that in normal men. There was a significant difference in distribution of haplotypes of the four SNPs between the two groups (P=0.01). Hapoltypes ACAC (11.1% vs. 6.6%, P=0.029) and ACGC (11.2% vs. 5.2%, P=0.003) increased significantly in azoospermic patients compared with controls.</p><p><b>CONCLUSION</b>The allele C of rs2057951 locus and haplotypes ACAC and ACGC of the four SNPs in PTAZ1 gene increased the susceptibility to azoospermia, suggesting that PATZ1gene may be associated with azoospermia.</p>

Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia.

Chromosomal abnormality and Y chromosome microdeletion are regarded as two frequent genetic causes associated with spermatogenic failure in Caucasian population. To investigate the distribution of the two genetic defects in Chinese patients with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 358 idiopathic infertile men, including 256 patients with azoospermia and 102 patients with severe oligozoospermia, and screening of AZF region microdeletion of Y chromosome by multiplex PCR was performed in those patients without detectable chromosomal abnormality and 100 fertile controls. Of 358 patients, 39(10.9%) were found to have chromosomal abnormalities in which Klinefelter's syndrome (47, XXY) was the most common chromosomal aberration. The incidence of sex chromosomal abnormality in patients with azoospermia was significantly higher than that in patients with severe oligozoospermia (12.1% vs 1%). Among the rest of the 319 patients with normal karyotype, 46 (14.4%) were found to have microdeletions in AZF region. The prevalence rates of AZF microdeletion was 15% and 13.1% in patients with azoospermia and severe oligozoospermia respectively. The microdeletion in AZFc was the most frequent deletion and all the microdeletions in AZFa were found in azoospermic patients. No microdeletion in AZF region was detected in fertile controls. In conclusion, chromosomal abnormality and AZF region microdeletion of Y chromosome might account for about 25% of Chinese infertile patients with azoospermia or severe oligozoospermia, suggesting the two abnormalities are important genetic etiology of spermatogenic failure in Chinese population and it is essential to screen them during diagnosis of male infertility before in vitro assisted fertilization by introcytoplasmic sperm injection.

DAZ1/DAZ2 cluster deletion mediated by gr/gr recombination per se may not be sufficient for spermatogenesis impairment: a study of Chinese normozoospermic men / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To explore the possible effect of the deleted in azoospermia (DAZ) copy cluster deletion on spermatogenesis in the Chinese population, the deletion of the azoospermia factor c (AZFc) region was analyzed in 346 normozoospermic men.</p><p><b>METHODS</b>Three DAZ single nucleotide variant loci and seven AZFc-specific sequence-tagged sites were examined with polymerase chain reaction (PCR)-restriction fragment length polymorphism and routine PCR.</p><p><b>RESULTS</b>Five (1.4%) of the normozoospermic men were found to have deletion of gr/gr-DAZ1/DAZ2. None of the men were found to have b2/b4-entire DAZ deletion.</p><p><b>CONCLUSION</b>The presence of gr/gr-DAZ1/DAZ2 deletion in five men with normozoospermia suggests that this deletion per se may not be sufficient for spermatogenic impairment in Chinese men.</p>

Possible association between 278C/A single nucleotide polymorphism of FKBP6 and idiopathic azoospermia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate 2 polymorphism sites in exon 3 and intron 2 of FKBP6 in Chinese population, while screening the gene mutations and polymorphisms in exons 3, 4 of FKBP6, and the association of these polymorphisms with azoospermia.</p><p><b>METHODS</b>Possible variations of exons 3, 4 and genotypes and frequencies of 2 polymorphic loci were examined by denaturing high-performance liquid chromatography(DHPLC) and PCR-restriction fragment length polymorphism(PCR-RFLP) technique in 177 azoospermia patients and 231 control individuals.</p><p><b>RESULTS</b>The observed allele frequencies conformed well to Hardy-Weinberg equilibrium. The frequency of 278A allele was significantly higher in controls than that in patients (P<0.05). C/T(s7797242) polymorphism was not found in either group and variations in exons 3, 4 were not detected.</p><p><b>CONCLUSION</b>278A polymorphism of FKBP6 gene was associated with idiopathic azoospermia, while C/T, 370G/A, 430G/C, 467T/C, 468G/A polymorphisms might be very rare in Chinese population.</p>