[Show abstract][Hide abstract] ABSTRACT: Mycoplasma bovis (M. bovis) is a major, but often overlooked, pathogen documented to cause respiratory disease, mastitis, and arthritis in cattle throughout China since 2008. Here, we report the development of a direct competitive enzyme-linked immunosorbent assay (Dc-ELISA) to detect M. bovis antibody.
We used a recombinant P48 protein and monoclonal antibody (mAb) 10E. MAb 10E, prepared against the recombinant P48 protein of M. bovis, identified all M. bovis strains with no cross-reactivity with other related pathogens. Coating micro plates with P48 protein instead of whole M. bovis cells as well as the use of mAb 10E produced a specific and sensitive Dc-ELISA for M. bovis antibody detection with a cut-off percent inhibition (PI) value of 32%. Compared with two commercial indirect ELISA (i-ELISA) kits, our Dc-ELISA offered a higher positive detection rate in 165 clinical bovine serum samples.
A rapid, sensitive, and reliable serological diagnosis method was developed for M. bovis, which can facilitate M. bovis surveillance, assisting researchers in understanding the ecology and epidemiology of M. bovis.
BMC Veterinary Research 02/2014; 10(1):42. DOI:10.1186/1746-6148-10-42 · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ɛ3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.Kidney International advance online publication, 11 September 2013; doi:10.1038/ki.2013.335.
Kidney International 09/2013; 85(2). DOI:10.1038/ki.2013.335 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Testis gene Znf230 may play a role in mammalian spermatogenesis according to previous reports. Deleting 5' important exons to block the formation of protein was a routine way in gene-knockout experiments. To investigate the physiological function of Znf230 gene, the mutant mice with disrupted exon 2 of Znf230 were generated in this study. Results showed that, mutant Znf230 mice were fertile and showed normal body, genitourinary organs, testes weights, and spermatid number but the litter size of the offspring reduced with unclear reasons. Hematoxylin and eosin staining showed that the testicular tissue of mutant mice was intact. Reverse transcriptase polymerase chain reaction analysis showed that two novel mutant transcripts appeared in the mutant mice: the short one including exon-1 and exon-3 to -6, the long one unexpectedly containing a partial sequence from the pPNT vector acting as a new exon 2. Bioinformatic analysis of the long transcript revealed that it might code a 24-kDa N-terminal mutant protein with the same 182 amino acids as that of the wild-type Znf230 in the C-terminus, indicating that the potential functional region of C3HC4-type RING finger was intact in mutant protein. Western blot and immunohistochemistry analyses also implied that this N-terminal mutation of Znf230 might not disrupt the possible role that wild-type Znf230 played in spermatogenesis. In summary, a potential exon structure in the targeting vector sequence involved in the expression of targeting Znf230 gene and disturbed the strategy of this gene-targeting experiment.
[Show abstract][Hide abstract] ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: PKD1 (16p13.3) and PKD2 (4q21). Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of PKD1 gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both PKD1 and PKD2 genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC).
Both PKD1 and PKD2 genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources.
A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication) were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65). About 69% (20/29) of the mutations are first reported with a recurrent mutation rate of 31%.
Mutation study of PKD1 and PKD2 genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.
BMC Medical Genetics 12/2011; 12(1):164. DOI:10.1186/1471-2350-12-164 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the possible association between single nucleotide polymorphisms (SNPs) in the miRNA-binding sites of spermatogenesis-related genes and idiopathic infertility in humans.
Research laboratory of a university hospital.
A total of 494 patients with azoospermia or severe oligozoospermia and 357 fertile controls were included in our study.
The 3' untranslated region sequences of 140 candidate genes for male infertility were analyzed using specialized algorithms including Pictar, miRanda, Targetscan, and RNAhybrid and 39 SNPs located at putative miRNA-binding sites were identified. The possible association of 6 putatively functional SNPs and male infertility was explored further with the use of case-control studies. The function of SNPs significantly associated with male infertility was analyzed by dual luciferase assay.
Significantly associated SNPs and their influence on gene expression.
Two SNPs from two genes (rs6631 of CGA and rs2303846 of CPEB1) were found to be associated with idiopathic male infertility. Functionally, the substitution of A by T in rs6631 results in decreased binding affinity of miR-1302 and overexpression of CGA in vitro.
Our results reveal for the first time that SNPs residing in miRNA-binding sites of CGA could influence expression of CGA and elevate the risk of spermatogenesis impairment.
Fertility and sterility 05/2011; 96(1):34-39.e7. DOI:10.1016/j.fertnstert.2011.04.053 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the predisposing background for the instability of CAG expansions of the HTT gene in a Chinese population.
Genotyping and haplotyping of CAG and CCG repeats of the HTT gene were carried out in 32 unrelated HD patients and 95 non-HD control individuals of Han origin, using capillary electrophoresis and DNA sequencing. The frequencies of different CCG repeats were compared between mutant and wild-type HTT genes. In controls, the comparison of the mean CAG repeat size was performed among different CCG repeats.
A total of five alleles of CCG repeats were distinguished, in which four were present in HD chromosomes. In the CCG alleles, (CCG)10 showed a higher frequency in mutant HTT genes relative to wild-type ones, and the highest mean CAG repeat size was observed in the (CCG)10 background. Additionally, a haplotype of (CAG)32-(CCG)10 was found in the control group.
Our findings indicate that HTT mutation is likely of multiple origins in the Chinese population. Among the origins, more new HTT mutations may arise from the (CCG)10 than from other CCG alleles, which suggests that the (CCG)10 allele may represent a predisposing background for CAG expansion in Chinese populations. Therefore, in comparison with Europeans, the significantly lower prevalence of Huntington's disease in Chinese individuals may not be due to the absence of the predisposing background for CAG expansion but instead may partly result from the lower frequency of the predisposing haplotype for CAG instability in the population.
Journal of the neurological sciences 11/2010; 298(1-2):57-60. DOI:10.1016/j.jns.2010.08.024 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A large number of testis-specific genes are involved in the complex process of mammalian spermatogenesis. Identification of these genes and their roles is important for understanding the mechanisms underlying spermatogenesis. Here we report on a novel human RING finger protein, ZNF645, which contains a C3HC4 RING finger domain, a C2H2 zinc-finger domain, and a proline-rich region, indicating that it has a structure similar to that of the c-Cbl-like protein Hakai. ZNF645 was exclusively expressed in normal human testicular tissue. Immunohistochemical analysis confirmed that ZNF645 protein was present in spermatocytes, round and elongated spermatids, and Leydig cells. Immunofluorescence staining of mature sperms further showed that the ZNF645 protein was localized over the postacrosomal perinuclear theca region and the entire length of sperm tail. An in vitro ubiquitination assay indicated that the RING finger domain of the ZNF645 protein had E3 ubiquitin ligase activity. Therefore, we suggest that ZNF645 might act as an E3 ubiquitin-protein ligase and play a role in human sperm production and quality control.
Asian Journal of Andrology 09/2010; 12(5):658-66. DOI:10.1038/aja.2010.54 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer/testis (CT) antigens exhibit highly tissue-restricted expression and are considered promising targets for cancer vaccines. Here we identified a novel CT gene ZNF645 which restrictively expresses in normal human testes and lung cancer patients (68.3%). To investigate the promoter methylation status of ZNF645, we carried out bisulfite genomic sequencing and found that the CpG island in its promoter was heavily methylated in normal lung tissues without the expression of ZNF645, whereas there was high demethylation in normal human testes and lung carcinoma tissues with its expression. Also ZNF645 could be remarkably activated in A549 and HEK293T cells treated by DNA demethylation agent 5'-aza-2'-deoxycytidine. And the dual luciferase assay revealed that the promoter activity of the ZNF645 was inhibited by methylation of the CpG island region. Therefore, we proposed that ZNF645 is a CT gene and activated in human testis and lung cancers by demethylation of its promoter region.
[Show abstract][Hide abstract] ABSTRACT: TSSK6 is a member of the testis-specific serine/threonine kinase family. Male Tssk6 knockout mice are infertile owing to spermatogenic impairment, including sperm count reduction, a decrease in motile sperm number and motility rates, and an increase in the number of sperms with abnormal morphology. We investigated the possible association between variations of the TSSK6 gene and spermatogenic impairment in humans. Mutation screening of TSSK6 was carried out in 519 patients with azoospermia (n = 273) or severe oligozoospermia (n = 246) and in 359 controls with normozoospermia by denaturing high-performance liquid chromatography and DNA sequencing. The frequencies of alleles and genotypes of gene polymorphism were compared between patients and controls. A novel triallelic polymorphism in TSSK6, c.822+126T>G/C, was identified. The frequencies of genotype TT and allele T were increased dramatically in infertile patients compared with controls, whereas genotype TG, allele G and allele C frequencies were significantly higher in controls than in patients. Further study revealed that the allele C frequency of controls was remarkably higher than that of patients with oligospermia. Our findings, for the first time, suggested an association of c.822+126T>G/C in TSSK6 with spermatogenic impairment in humans in which allele T may be a risk factor for male infertility, while alleles C and G may decrease susceptibility to male infertility.
Asian Journal of Andrology 03/2010; 12(2):234-9. DOI:10.1038/aja.2009.80 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To standardize the experimental procedure of the gene test for autosomal dominant cerebellar ataxias (ADCA), and provide the basis for quantitative criteria of the dynamic mutation of spinocerebellar ataxia (SCA) genes in Chinese population.
Genotyping of the dynamic mutation loci of the SCA1, SCA2, SCA3, SCA6 and SCA7 genes was performed, using florescence PCR-capillary electrophoresis followed by DNA sequencing, to investigate the variation range of copy number of CAG tandem repeat of the genes in 263 probands of ADCA pedigrees and 261 non-related normal controls. Based on the sequencing result, the bias of the CAG copy number estimation using capillary electrophoresis with different DNA controls was compared to analyze the technical detailes of the electrophresis method in testing the dynamic mutation sites.
PCR products containing dynamic mutation loci of the SCA genes showed significantly higher mobility than that of molecular weigh marker with relatively balanced GC content. This was particularly obvious in the SCA2, SCA 6 and SCA7 genes whereas the deviation of copy number could be corrected to +/-1 when known CAG copy number fragments were used as controls. The mobility of PCR products was primarily related to the copy number of CAG repeat when the fragments contained normal CAG repeat. In the 263 ADCA pedigrees, 6 (2.28%) carried SCA1 gene mutation, 8 (3.04%) had SCA2 mutation and 81 (30.80%) harbored SCA3 mutation. The gene mutation of SCA6 and SCA7 was not found. The normal variation range of the CAG repeat was 17-36 copies in SCA1 gene, 13-30 copies in SCA2, 14-39 copies in SCA3, 6-16 copies in SCA6 and 6-13 copies in SCA7. The heterozygosity was 76.1%, 17.7%, 74.4%, 72.1% and 41.3%, respectively. The mutation range of the CAG repeat was 49-56 copies in SCA1 gene, 36-41 copies in SCA2, 59-81 copies in SCA3. Neither homozygous mutation of an SCA gene nor double heterozygous mutation of the SCA genes was observed in the study.
The copy number of the CAG repeat in SCA genes could be calculated accurately based on the result of florescence PCR-capillary electrophoresis when limited amount of known repeat copy number controls were used. Our result supported that the notion that SCA3 gene mutation was the most common cause for ADCA, and the obtained data would be helpful for establishing quantitative criteria of the dynamic mutation of the SCA genes in Chinese.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 12/2009; 26(6):626-33. DOI:10.3760/cma.j.issn.1003-9406.2009.06.005
[Show abstract][Hide abstract] ABSTRACT: Tssk2, a member of the testis-specific serine/threonine kinase (TSSK) family, is expressed predominantly in the testis and is crucial for the formation and function of sperm cells in the mouse. Targeted deletion of Tssk1 and Tssk2 in male chimeric mice caused infertility because of haploinsufficiency of the genes. Therefore, it is reasonable to postulate that mutations in the human homolog TSSK2 gene may also play a role in impaired spermatogenesis in humans. To explore the possible association between mutations in the TSSK2 gene and idiopathic infertility in humans, mutation screening of the gene in 494 patients with azoospermia or severe oligozoospermia and 357 fertile controls was performed using denaturing high-performance liquid chromatography and DNA sequencing. As a result, 4 single-nucleotide transitions were identified, including c.80A>G (rs3747052), c.774C>T (rs1052756), c.839C>T (rs1052763), and c.1026G>A (rs1052773). Among them, significant differences in polymorphism frequencies were observed of c.80A>G (rs3747052) and c.774C>T (rs1052756) between the patients and controls; the allele G of c.80A>G (rs3747052) and allele T of c.774C>T (rs1052756) seem to be risk factors for the development of spermatogenic impairment, suggesting that the TSSK2 gene may be associated with male idiopathic infertility in humans.
Journal of Andrology 11/2009; 31(4):388-92. DOI:10.2164/jandrol.109.008466 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CD24 is markedly overexpressed in ovarian cancer and plays a critical role in ovarian cancer survival and metastasis, rendering it an interesting target for anti-tumor therapy. Using short hairpin RNA (shRNA) targeting CD24, we aimed to investigate the anti-tumor efficacy of CD24 knockdown in ovarian cancer cells in vitro and in vivo.
CD24 shRNA vector (CD24-shRNA) and empty plasmid vector (EP) were transfected into ovarian cancer SKOV3 cells and the knockdown efficacy assessed by Western blot analysis. The effects of CD24 knockdown in SKOV3 cells in vitro, including cell viability and apoptosis, were determined using methyl thiazolyl blue tetrazolium bromide (MTT), flow cytometry and propidium iodide (PI) staining assays. The effects in vivo of CD24 knockdown on angiogenesis, cell proliferation and apoptosis were assessed using immunohistochemistry against CD31, proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assays.
Transfection of CD24-shRNA effectively down-regulated CD24 expression in vitro and in vivo. Administration of CD24-shRNA into nude mice bearing ovarian cancer significantly suppressed tumor volume growth.
Knockdown of CD24 expression by CD24-shRNA significantly inhibited cell viability and induced apoptosis of SKOV3 cells in vitro. Administration with CD24-shRNA in vivo suppressed tumor volume increase by microvessel density (MVD) decrease, cell proliferation inhibition and apoptosis induction. All the data suggested that knockdown of CD24 by shRNA might be a potential therapeutic approach against human ovarian cancer.
[Show abstract][Hide abstract] ABSTRACT: The phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in ovarian cancer cell survival and proliferation. The aim of this study was to determine whether the suppression of the PI3K catalytic subunit p110alphainhibits the growth of ovarian cancer cells in vitro and in vivo.
The short hairpin RNA (shRNA) was used to knock down the expression of p110alpha in SKOV3 human ovarian cancer cells. The effects of shRNA on cell viability and apoptosis in vitro were assessed using the MTT assay and flow-cytometric analysis. Furthermore, the growth inhibition capacity of shRNA on ovarian carcinoma xenografts was tested in nude mice. Tumor cell proliferation, apoptosis and angiogenesis were measured by proliferating cell nuclear antigen, TUNEL and CD31 immunohistochemistry, respectively.
Using sequence-specific shRNA, we have silenced the expression of p110alpha in SKOV3 cells. shRNA-mediated knockdown of p110alpha correlated in vitro with decreased cell viability and increased apoptosis. Furthermore, inhibition of p110alpha significantly delayed the growth of ovarian carcinoma xenografts, and ultimately resulted in decreased cell proliferation, induction of apoptosis as well as a reduction in microvessel density.
Our findings suggest that shRNA-directed targeting of p110alpharaises the potential of its application in human ovarian cancer therapy.
[Show abstract][Hide abstract] ABSTRACT: DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.
Journal of Andrology 05/2009; 31(2):163-8. DOI:10.2164/jandrol.108.007187 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A residue depletion study was performed with high-performance liquid chromatography (HPLC) to determine a withdrawal period of imidocarb (IMD) in swine tissues. The drug was administered intramuscularly (im) at the dose of 2.0 mg kg(-1) of body weight (bw) once a day for 3 days. Samples of muscle, fat, liver, kidney, and injection site muscle from 5 pigs were collected on 7, 14, 28, and 56 days after the last administration. Quantitative analysis of IMD was conducted by HPLC-UV at 260 nm after liquid-liquid extraction. The limit of detection (LOD) of the method was 0.1 microg g(-1) for liver and kidney and 0.05 microg g(-1) for muscle and fat, respectively. Mean recoveries of IMD in all fortified samples at a concentration range of 0.1-25 microg g(-1) were 69.5-89.3%, with a coefficient of variation (CV) below 13.3%. In swine, the highest drug levels occurred in liver and kidney during the whole study period, suggesting that these tissues are targets for residues. IMD concentrations in all examined tissues were below the accepted maximum residue limits (MRLs) recommended by the Committee for Veterinary Medical Products (CVMP) of the European Medical Evaluation Agency (EMEA) at 54 days post-treatment.
Journal of Agricultural and Food Chemistry 03/2009; 57(6):2324-8. DOI:10.1021/jf803251j · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we inhibited the expression of VEGF by short hairpin RNA (shRNA) in SKOV3 ovarian cancer cells in vitro and in vivo to explore the antitumor efficacy of shRNA in ovarian cancer cells.
ShRNA targeting VEGF was cloned into pGenesil-2 plasmid vector and then transfected into SKOV3 ovarian cancer cells using liposome. Silencing of VEGF expression was measured by RT-PCR and ELISA assays. Furthermore, the growth inhibition capacity of shRNA on SKOV3 intraperitoneal ovarian carcinomatosis was tested in nude mice. Tumor weight was measured. Microvessel density, number of apoptotic cells and proliferation index in tumor tissues were assessed by CD31, TUNEL and PCNA immunostaining.
shRNA targeting VEGF significantly silenced VEGF expression in SKOV3 ovarian cancer cells, confirmed by RT-PCR and ELISA assays (p < 0.05). In vivo, the shRNA reduced tumor weight by approximately 60.3% compared with control groups (p < 0.05), accompanied with angiogenesis inhibition (p < 0.01) and apoptosis induction (p < 0.01).
Our data indicated that shRNA-mediated silencing of VEGF might be a promising therapeutic strategy against ovarian cancer by reducing angiogenesis and inducing apoptosis.
[Show abstract][Hide abstract] ABSTRACT: Znf230, the mouse homologue of the human spermatogenesis-related gene, ZNF230, has been cloned by rapid amplification of cDNA ends (RACE). This gene is expressed predominantly in testis, but its expression in different testicular cells and spermatogenic stages has not been previously analyzed in detail. In the present study, the cellular localization of the Znf230 protein in mouse testis and epididymal spermatozoa was determined by RT-PCR, immunoblotting, immunohistochemistry and immunofluorescence. It is primarily expressed in the nuclei of spermatogonia and subsequently in the acrosome system and the entire tail of developing spermatids and spermatozoa. The results indicate that Znf230 may play an important role in mouse spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization.
[Show abstract][Hide abstract] ABSTRACT: The testis-specific serine/threonine kinase (TSSK) family is a specific kinase group with exclusive or dominant expression in testis and involvement in spermatogenesis and male infertility. TSSK4 is a newly identified member of the TSSK family. In order to investigate the possible relationships between variations, including mutations and polymorphisms of the TSSK4 gene and impaired spermatogenesis in humans, mutation screening of this gene in 372 patients with azoospermia or severe oligospermia and 220 controls was performed. In total, 4 novel single nucleotide changes including c.679G>A, c.987+108G>A, c.-155C>G and c.765C>A were discovered. The latter 2 variations were found only in patients, not in controls. Bioinformatics analysis suggested that allele A of c.765C>A could decrease the activity of pre-mRNA splicing of TSSK4. The frequency of allele A of c.679G>A was significantly higher in controls than in patients. On the contrary, allele A of c.987+108G>A was remarkably increased in patients compared with controls. Our investigation of TSSK4, a potentially important testicular gene, in Chinese infertile and control men identified the association of some single nucleotide polymorphisms in this gene with male infertility.
Journal of Andrology 07/2008; 29(4):374-8. DOI:10.2164/jandrol.107.004598 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the possible association of the MSY2 gene with idiopathic male infertility in humans.
Mutation screening was performed in 326 patients with azoospermia or severe oligospermia and 210 controls by denaturing high-performance liquid chromatography and DNA sequencing. The differences in genotype and allele distribution in the two groups were evaluated. The Haploview program, version 4.0, was used to perform linkage disequilibrium and haplotype analysis.
A total of eight variations, including five single nucleotide polymorphisms and three rare single nucleotide changes, were identified. The frequencies of allele C of c.187T>C and allele G of c.1095+16A>G were significantly greater in the controls than in the patients, and both seemed to play a protective role against spermatogenic impairment. The haplotype GTCTA, consisting of the five single nucleotide polymorphisms, might be a genetic risk factor for development of male infertility.
The results of our study suggest that some polymorphisms of the MSY2 gene might be associated with impaired spermatogenesis and that the gene could also be involved in modifying the susceptibility to idiopathic spermatogenic impairment in humans.