Risk Of Idiopathic Male Infertility Research Articles

Association of Functional Genetic Variations in Uric Acid Transporters with the Risk of Idiopathic Male Infertility: A Genetic Association Study and Bioinformatic Analysis.

Uric acid plays an important role in sustaining and improving sperm morphology, viability, and motility. It is known that SLC2A9 and ABCG2 protein are the main urate transporter and genetic variations in these genes could be associated with the levels of serum uric acid. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) SLC2A9-rs16890979, SLC2A9-rs3733591, ABCG2-rs2231142, and ABCG2-rs2231137 with male infertility. Additionally, the correlation of these SNPs with the uric acid level in seminal plasma of infertile men was examined. Subsequently, an in silico analysis was performed. In a case-control study, 193 infertile and 154 healthy controls were recruited. After semen sample collection, the uric acid level of seminal plasma was measured by a commercial kit. After genomic DNA extraction from sperm samples, SNPs genotyping was performed by PCR-RFLP method. Lastly, the effects of SNPs on the SLC2A9 and ABCG2 gene function were evaluated by bioinformatics tools. The genetic association study revealed that there are significant associations between rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations and increased risk of male infertility. Also, these variations were associated with oligozoospermia and teratozoospermia, and sometimes with asthenozoospermia. Also, we found that four studied SNPs could be associated with a decreased level of uric acid of seminal plasma in teratozoospermia and asthenozoospermia. Bioinformatic analysis revealed that the mentioned polymorphisms could affect molecular aspects of SLC2A9 and ABCG2 genes. In this preliminary study, the rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations could be considered as genetic risk factors for male infertility by interfering with the uric acid level of seminal plasma.

MP01-08 THE TESTIS AND EPIDIDYMIS-SPECIFIC WFDC LOCUS GENES ARE REQUIRED FOR MALE FERTILITY

You have accessJournal of UrologyCME1 Apr 2023MP01-08 THE TESTIS AND EPIDIDYMIS-SPECIFIC WFDC LOCUS GENES ARE REQUIRED FOR MALE FERTILITY Katarzyna Kent, Kimia Bakhshandeh, Kanchan Yadav, Martin Matzuk, Larry Lipshultz, and Thomas Garcia Katarzyna KentKatarzyna Kent More articles by this author , Kimia BakhshandehKimia Bakhshandeh More articles by this author , Kanchan YadavKanchan Yadav More articles by this author , Martin MatzukMartin Matzuk More articles by this author , Larry LipshultzLarry Lipshultz More articles by this author , and Thomas GarciaThomas Garcia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite 96 million years of evolution separating humans and rodents, 11 closely-related reproductive tract-specific genes in human—SPINT3, WFDC6, EPPIN, WFDC8, WFDC9, WFDC10A, WFDC11, WFDC10B, WFDC13, SPINT4, and WFDC3—and the 13 reproductive tract-specific orthologs in mouse (listed below), form highly conserved syntenic gene clusters indicative of a conserved, combined critical functions. Further, despite significant progress towards a non-hormonal male contraceptive targeting the protein encoded by one of these genes, EPPIN, and associations found between gene mutations in EPPIN and an increased risk of idiopathic male infertility, neither EPPIN nor any of the closely-related genes within the WFDC locus have been explored functionally through genetically manipulated mouse models. To clarify the involvement of these genes in male fertility, we generated and studied mice lacking a combined total of 13, 10, 5, or 4 genes within the conserved gene cluster. METHODS: Custom gRNAs were assembled into ribonucleoprotein complexes with Cas9 nuclease and electroporated into zygotes harvested from superovulated B6D2F1 females. Embryos were cultured overnight to the 2-cell stage before being transferred into the oviducts of pseudopregnant ICR mice. Founder mutations in pups born were identified by PCR and Sanger sequencing. RESULTS: Founder mouse containing a -173.2 kb deletion, corresponding to deletion of all 13 genes (Spint3, Wfdc6a, Eppin, Wfdc8, Wfdc6b, Wfdc16, Wfdc9, Wfdc10, Wfdc11, Wfdc13, Spint4, Spint5, Wfdc3) were expanded for further study. Likewise, founder mice containing either a -115.4 kb deletion (10 genes deleted from Spint3 to Wfdc13), a -46.7 kb deletion (5 genes deleted from Wfdc16 to Wfdc13), and a -28.8 kb deletion (4 genes deleted from Wfdc6a to Wfdc6b) were expanded for further study. We also generated and expanded a single knockout of Wfdc3. The 13 gene, 10 gene, and 4 gene knockouts were all infertile due to a block of spermatogenesis and azoospermia. The 5 gene knockouts were infertile due to asthenozoospermia, while the single knockout of Wfdc3 was fertile with no obvious reproductive phenotype. CONCLUSIONS: Our knockout mouse studies, the first of its kind to study an entire locus of closely related genes, have at last clarified the functional requirement of WFDC locus genes in male fertility, which has implications towards improved clinical diagnosis of men with infertility. Source of Funding: This study has been supported by National Institutes of Health R01 HD106056 and R01 HD095341 (to T.X.G.) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e4 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katarzyna Kent More articles by this author Kimia Bakhshandeh More articles by this author Kanchan Yadav More articles by this author Martin Matzuk More articles by this author Larry Lipshultz More articles by this author Thomas Garcia More articles by this author Expand All Advertisement PDF downloadLoading ...

Association of PRMT6, PEX10 and SOX5 genetic variants with idiopathic male infertility: Evidence from North Macedonian population and an updated meta-analysis

PRMT6, PEX10 and SOX5 genetic variants were identified as male infertility-associated loci in a genome-wide association study and further validated in various populations. Still, the results of previous case-control studies varied, which could be due to differences in participants? ethnic backgrounds. The main purpose of the present study was to evaluate the supposed association of these variants with idiopathic male infertility in North Macedonian population. Furthermore, we aimed to conduct the systematic quantitative data synthesis which includes the results of previous studies on the same issue in other European and non-European populations. A total of 137 men from North Macedonia diagnosed with idiopathic infertility and 130 age-matched fertile controls were included in the present case-control study. PCR-RFLP method was used for genotyping. Meta-analysis was performed by OpenMeta-analyst statistical software. Variants rs10842262 in SOX5, rs2477686 in PEX10 and rs12097821 in PRMT6 showed the lack of statistically significant differences in genotype distributions between men diagnosed with idiopathic infertility and the control group. Still, rs10842262 allele G frequency was significantly increased in men with poor sperm concentration (P= 0.024, OR = 2.10, 95%CI 1.08-4.06). Meta-analysis further showed the association of rs10842262 and rs12097821 with the risk of idiopathic male infertility. Our results obtained in North Macedonian population supported the previous reports on the involvement of rs10842262 in the genetic basis of male infertility. The meta-analysis confirmed the association of rs10842262 and rs12097821 with male infertility occurrence. Still, additional studies are needed to support the present findings.

AURKC Gene Polymorphism (rs58264281) Associated with Idiopathic Male Infertility Risk in Northeast of Iran: A Case-Control Study

Background: Infertility is a major public health and social problem in human reproduction that is known as a multifactorial complex disorder. Genetic background and mutations and single nucleotide polymorphisms (SNPs) on the genes involved in sperm development are the important causes of male infertility. Objectives: In this study, we evaluated the association of AURKC gene polymorphism (rs58264281) and idiopathic male infertility in the Iranian Azeri population. Methods: This study was performed among 100 men with idiopathic infertility (case group) and 100 healthy men with successful fertility (control group) from East Azerbaijan, Iran. Genomic DNA extraction was carried out from peripheral blood samples by the proteinase K method. Genotype analysis was conducted by the tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS PCR). SPSS version 21 was used for the analysis of the obtained data. Results: We observed that the CA and AA genotypes were significantly increased in patients with infertility as compared to healthy controls. Our results demonstrated that the mutant allele of AURKC gene polymorphism (rs58264281) was a significant risk factor in male infertility. Conclusions: We suggested a significant correlation between the AURKC gene rs58264281 polymorphism and male infertility in the Iranian Azeri population. However, further studies are required among other ethnicities, races, and geographic areas with larger sample sizes.

Association study between single-nucleotide variants rs12097821, rs2477686, and rs10842262 and idiopathic male infertility risk in Serbian population with meta-analysis.

A genome-wide association study conducted in the Han Chinese population identified three single nucleotide variants rs12097821, rs2477686, and rs10842262 as being significantly associated with non-obstructive azoospermia. Our aim was to evaluate the possible association between these susceptibility loci and idiopathic male infertility risk in the Serbian population. A case-control study was conducted on 431 male individuals from the Serbian population divided into two groups. The case group consisted of 208 males diagnosed with oligoasthenozoospermia or non-obstructive azoospermia, while the control group involved 223 fertile men who have fathered at least one child. According to codominant (Pcodom = 0.048, ORcodom = 0.57, 95%CI 0.35-0.92) and overdominant (Poverdom = 0.017, ORoverdom = 0.62, 95%CI 0.42-0.92) genetic models, rs10842262 was found to be associated with male infertility. Stratifying infertile men according to diagnosis yielded statistically significant results for non-obstructive azoospermia cases under multiple genetic models (Pcodom = 0.038, ORcodom = 0.47, 95%CI 0.26-0.85; Pdom = 0.031, ORdom = 0.53, 95%CI 0.30-0.94; Poverdom = 0.016, ORoverdom = 0.55, 95%CI 0.33-0.90). Minor allele C of rs2477686 genetic variant was shown to be associated with the reduced risk of oligoasthenozoospermia under the log-additive genetic model (P = 0.03, OR = 0.69, 95%CI 0.50-0.97). The results of the meta-analysis indicate both rs2477686 and rs10842262 to be associated with male infertility. Our results show variants rs2477686 and rs10842262 to be significantly associated with male infertility in the Serbian population. Nevertheless, case-control studies in other populations are needed to validate their association with infertility in males diagnosed with oligoasthenozoospermia and non-obstructive azoospermia.

Contribution of MTR A2756G polymorphism and MTRR A66G polymorphism to the risk of idiopathic male infertility.

Background:Methionine synthase reductase gene (MTRR A66G) polymorphism and methionine synthase gene (MTR A2756G) polymorphism have shown an association with idiopathic male infertility risk in several ethnic populations. However, their small sample sizes and inconsistent outcomes have prevented strong conclusions. We performed a meta-analysis with published studies to evaluate the associations of the 2 single nucleotide polymorphisms (SNPs) and idiopathic male infertility risk.Methods:A thorough literature search was performed up to Jun 21, 2019 with Medline, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medical literature (CBM), China Science and Technology Journal Database (VIP), and Chinese literature (Wan Fang) databases. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of associations.Results:Seventeen studies including 3269 cases and 3192 controls met the inclusion criteria. Our meta-analysis showed that the MTR A2756G mutation may contribute to genetic susceptibility to the risk of idiopathic male infertility in Non-Asians, but not to Asian population, whereas the MTRR A66G polymorphism may be unrelated to idiopathic male infertility in both Non-Asian and Asian populations. In the stratified analysis by infertility type, the MTR A2756G polymorphism was a risk factor for both non-obstructive azoospermia (NOA) and oligoasthenoteratozoospermia (OAT) patients. However, the MTRR A66G polymorphism is associated with risk for OAT in Asian, but not in Non-Asian population.Conclusion:This meta-analysis suggested that the MTR A2756G and MTRR A66G polymorphisms were risk factors for idiopathic male infertility. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.

IL-1RA VNTR and IL-1α 4845G>T polymorphisms and risk of idiopathic male infertility in Iranian men: A case-control study and an in silico analysis.

This study aimed to investigate the association of IL-1RA VNTR and IL-1α 4845G>T polymorphisms with idiopathic male infertility followed by an in silico analysis. In a case-control study, we collected blood samples from 230 infertile and 230 healthy men. Genotyping of IL-1RA VNTR was performed by PCR whereas IL-1α 4845G>T was genotyped by polymerase chain reaction-restriction fragment length polymorphism. An in silico approach was employed for the detection of IL-1RA VNTR and IL-1α 4845G>T effects on some molecular aspects of IL-1RA and IL-1α respectively. The result of our genetic association study for IL-1α 4845G>T revealed that there was a significant association between GT genotype, TT genotype, T allele and idiopathic male infertility. Although there was no significant association between IL-1RA VNTR and male infertility in the overall analysis. However, subgroup analysis revealed that the subjects with VNTR 4R/5R genotype were at a higher risk of oligozoospermia. Furthermore, 4845TT genotype, and 4845T allele were associated with oligozoospermia, asthenozoospermia and nonobstructive azoospermia. Bioinformatics analysis showed that IL-1RA VNTR may affect the splicing pattern of IL-1RA. Moreover, IL-1α 4845G>T has a significant effect on RNA structure and protein function. Based on our findings, both IL-1RA VNTR and IL-1α 4845G>T polymorphisms could be considered as potential biomarkers for screening of susceptible individuals.

IL-1ɑ C376A Transversion Variant and Risk of Idiopathic Male Infertility in Iranian Men: A Genetic Association Study.

BackgroundIL-1α produced by Sertoli cells is considered to act as a growth factor for spermatogonia. In this study, we investigated the association of the C376A polymorphism in IL-1α with male infertility in men referring to the Kashan IVF Center.Materials and MethodsIn this case-control study, 2 ml of blood was collected from 230 fertile and 230 infertile men. After DNA extraction, the C376A variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the molecular effects of the C376A transversion were analysed using bioinformatics tools.ResultsA significant association was observed between the homozygous genotype CC with male infertility [odds ratio (OR)=1.97, 95% confidence interval (CI)=1.14-3.41, P=0.016)]. Carriers of C (AC+CC) showed a similar risk for male infertility (OR=1.78, 95% CI=1.06-2.99, P=0.030). Also, allelic analysis showed that the C allele is associated with male infertility (OR=1.43, 95% CI=1.09-1.88, P=0.011). In sub-group analysis, we found that the AC genotype is associated with asthenozoospermia (OR=2.38, 95% CI=1.03-5.53, P=0.043). In addition, carriers of C were at high risk for asthenozoospermia (OR=2.25, 95% CI=1.01-4.10, P=0.047). Also, C allele was significantly associated with oligozoospermia (OR=1.44, 95% CI=1.01-2.06, P=0.049) and non-obstructive azoospermia (OR=1.67, 95% CI =1.04-2.68, P=0.034). Finally, in silico analysis showed that the C376A polymorphism could alter splicing especially in the acceptor site.ConclusionThis is the preliminary report on the association of IL-1α C376A polymorphism with male infertility in the Kashan population. This association shows that the IL-1α gene may be a biomarker for male infertility, and therefore needs additional investigations in future studies to validate this.

Association between methylenetetrahydrofolate reductase (MTHFR) gene promoter hypermethylation and the risk of idiopathic male infertility.

Epigenetics has become a major field of reproductive medicine after the epigenetic regulation of gene expression was discovered. The aim of this study was to find out whether or not methylenetetrahydrofolate reductase (MTHFR) gene promoter hypermethylation in the spermatozoa of men who were offered assisted reproduction is associated with idiopathic male infertility. Sperm DNAs from 40 idiopathic infertile men with normozoospermia and 40 controls consisting of healthy fertile men were isolated. Following the modification of DNAs by sodium bisulphite, the methylation status of the MTHFR gene promoter was quantified by pyrosequencing. No significant differences were observed between the clinical characteristics of patients and controls. The percentage of MTHFR promoter methylation in infertile men with normozoospermia (11%) was significantly higher than that in the healthy control (4.3%) group (p=.01). A 9.5% of methylation level was determined via receiver operator characteristic (ROC) analysis as the cut-off value. There were 21 (53%) hypermethylated men among the infertile men and 2 (5%) in the control group (p=.0001). The intragroup analysis of the infertile group did not reveal any statistically significant differences in terms of overall clinical characteristics between hyper- and normo-methylated infertile men. Our results suggest that epigenetic silencing (hypermethylation) of MTHFR could result in an elevated risk of male infertility.

Analysis of XRCC1 Arg194Trp polymorphism and the risk of idiopathic male infertility

Analysis of XRCC1 Arg194Trp polymorphism and the risk of idiopathic male infertility

Common SNP in hsa-miR-196a-2 increases hsa-miR-196a-5p expression and predisposes to idiopathic male infertility in Chinese Han population.

MicroRNA plays an important role in spermatogenesis. Whether pre-miRNAs polymorphisms are associated with idiopathic male infertility remains obscure. In this study, 1378 idiopathic infertile males and 486 fertile controls were included between 2006 and 2014. Genotype of three polymorphisms (hsa-mir-146a rs2910164, hsa-mir-196a-2 rs11614913, and hsa-mir-499 rs3746444) and expression of miRNA in seminal plasma were examined by TaqMan method. The role of hsa-miR-196a-5p in cell proliferation, apoptosis and cell cycle were also examined in GC-2 cells. Our results demonstrated that rs11614913 of hsa-miR-196a-2 was significantly associated with idiopathic infertility (TT vs. CT: P = 0.014; TT vs. CC: P = 0.005; TT vs. CT + CC: P = 0.003). In following stratified analysis, we found that rs11614913 exhibited a significantly higher risk of asthenospermia, oligozoospermia and azoospermia. However, no significant association was observed between the other two polymorphisms and idiopathic male infertility risk. In a genotype-expression correlation analysis, rs11614913 CC was significantly associated with elevated expression of hsa-miR-196a-5p (P < 0.05). Additionally, apoptosis levels were significantly increased in hsa-miR-196a-5p mimic treated GC-2 cells, while decreased in hsa-miR-196a-5p inhibitor treated GC-2 cells. Our data revealed a significant relationship between hsa-miR-196a-2 polymorphism and idiopathic male infertility.

The association of ApE1 -656T>G and 1349T>G polymorphisms and idiopathic male infertility risk.

In spite of variety studies in understanding of human reproductive and fertility, the underlying causes of male infertility remains undefined in about 50 % of cases. The polymorphism studies have a crucial role in diseases recognizing. Human apurinic/apyrimidinic endonuclease 1 (ApE1) is a multifunctional protein that has an important role in the base excision repair pathway. The present study was aimed to evaluate whether two polymorphisms -656T>G and 1349T>G ApE1 are related with the susceptibility to idiopathic male infertility. Samples were collected from 180 patients diagnosed with idiopathic male infertility and 120 control subjects and genotyped by tetra-primer amplification refractory mutation system PCR. We observed a significant difference in genotype distributions of -656T>G ApE1 polymorphism between infertile patients and controls (P = 0.0001). Our findings indicated individuals with the variant TG genotypes had a significant increased risk of idiopathic male infertility (OR 1.84, 95 % CI 1.09-3.11, P = 0.021), whereas the significant association between the 1349T>G polymorphism and idiopathic male infertility risk was not observed (P = 0.2). Our data suggest that the -656T>G ApE1 polymorphism may be associated with increased risk of idiopathic male infertility. Larger studies with more patients and controls are needed to confirm the results.

The association between DAZ T > C polymorphism and idiopathic male infertility risk in north of Iran

THE ASSOCIATION BETWEEN DAZ T > C POLYMORPHISM AND IDIOPATHIC MALE INFERTILITY RISK IN NORTH OF IRAN, by S. P. Hadiyan, F. Mashayekhi*, Z. Salehi (Department of Biology, Faculty of sciences, University of Guilan, Rasht, Iran; *e-mail: umistbiology@yahoo.co.uk).

The association between the DAZ T &gt; C polymorphism and idiopathic male infertility risk in the north of Iran

The association between the DAZ T &gt; C polymorphism and idiopathic male infertility risk in the north of Iran

The association study between Eppin gene polymorphisms and idiopathic male infertility

To explore the correlation between four tagSNPs of Eppin gene (rs6124715, rs2231829, rs2227290 and rs11594) and the risk of idiopathic male infertility in the Chinese Han population. A total of 473 confirmed infertile patients (from March 2005 to March 2007) and 198 fertile male controls (March 2005 to February 2009) were selected from two hospitals in Nanjing. All the subjects were Han Chinese and came from Nanjing or its surrounding areas. 5 ml peripheral blood was drawn from each subject with informed consent. Four tagSNPs (rs6124715, rs2231829, rs2227290 and rs11594) in Eppin gene were analyzed by the PCR-restriction fragment length polymorphisms (PCR-RFLP) method. The serum testosterone level was evaluated by radioimmunoassay (RIA). The genotype frequencies of AA,AC and CC at rs11594 were 76.3% (361/473), 20.1% (95/473) and 3.6% (17/473) respectively in the case group, while the frequencies in the control group were 75.3% (149/198), 24.2% (48/198), 0.5% (1/198) respectively, the differences were statistically significant (χ² = 7.73, P = 0.021), the CC genotype carriers had an increased risk of male infertility (OR = 7.02, 95% CI:0.93-53.19). In the combined genotype analysis, the haplotype CTGA carriers has significantly lower onset risk (OR = 0.18, 95% CI:0.06-0.53). In the two groups, the frequencies and the risk of male infertility were no statistically significant in rs6124715, rs2231829 and rs2227290 genotype. The Eppin gene polymorphisms were correlated to the susceptibility to idiopathic male infertility. Among them, CC genotype at rs11594 could increase the risk of idiopathic male infertility.

AB210. The cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: a meta-analysis

Meta-analysis Polymorphism Studies of the relationship between male infertility and CYP1A1 polymorphisms are inconclusive. To drive a more precise estimation, we performed a meta-analysis based on 1,060 cases and 1,225 controls from 7 published case-control studies. PubMed and CNKI literature search were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of CYP1A1*2A genotype was significantly associated with susceptibility to idiopathic male infertility. Further stratified analysis by ethnicity showed notable association between the polymorphism and risk of idiopathic male infertility in Asians. In conclusion, these results support that the CYP1A1*2A genotype polymorphism mainly contributes to idiopathic male infertility susceptibility in Asians but not in Caucasians.

Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases the risk of idiopathic male infertility

N-acetyltransferase (NAT2) is a phase-II xenobiotic-metabolizing enzyme participating in the detoxification of toxic arylamines, aromatic amines and hydrazines. The present study was designed to investigate whether two common single-nucleotide polymorphisms (SNP) of the NAT2 gene (481C>T, rs1799929; 590G>A, rs1799930) are associated with susceptibility to idiopathic male infertility and to assess if the risk is modified by oxidant and antioxidant exposures. A total 430 DNA samples (203 infertile patients and 227 fertile men) were genotyped for the polymorphisms by PCR and restriction fragment length polymorphism. No association was found between the NAT2 polymorphisms and idiopathic male infertility. However, gene–environment interaction analysis revealed that a low-acetylation genotype, 590GA, was significantly associated with increased disease risk in men who had environmental risk factors such as cigarette smoking (OR 1.71, 95% CI 1.02–2.87, P = 0.042), alcohol abuse (OR 2.14, 95% CI 1.08–4.27, P = 0.029) and low fruit/vegetable intake (OR 1.68, 95% CI 1.01–2.79, P = 0.04). This pilot study found, as far as is known for the first time, that the polymorphism 590G>A of NAT2 is a novel genetic marker for susceptibility to idiopathic male infertility, but the risk is potentiated by exposure to various environmental oxidants.

Association between 3801T&gt;C Polymorphism of CYP1A1 and Idiopathic Male Infertility Risk: A Systematic Review and Meta-Analysis

BackgroundEpidemiological studies have evaluated the association between 3801T>C polymorphism of CYP1A1 gene and the risk for idiopathic male infertility, but the results are inconclusive. We aimed to derive a more precise estimation of the relationship by conducting a meta-analysis of case-control studies.MethodsThis study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase and CNKI databases were searched through November 2013 to identify relevant studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association between CYP1A1 3801T>C polymorphism and idiopathic male infertility risk. Q-test was performed to evaluate between-study heterogeneity and publication bias was appraised using funnel plots. Sensitivity analyses were conducted to evaluate the robustness of meta-analysis findings.ResultsSix studies involving 1,060 cases and 1,225 controls were included in this meta-analysis. Overall, significant associations between 3801T>C polymorphism and idiopathic male infertility risk were observed in allelic comparison (OR = 1.36, 95% CI: 1.01–1.83), homozygous model (OR = 2.18, 95% CI: 1.15–4.12), and recessive model (OR = 1.86, 95% CI: 1.09–3.20), with robust findings according to sensitivity analyses. However, subgroup analyses did not further identify the susceptibility to idiopathic male infertility in all comparisons. Funnel plot inspections did not reveal evidence of publication bias.ConclusionsThe current meta-analysis provides evidence of a significant association between CYP1A1 3801T>C polymorphism and idiopathic male infertility risk. Considering the limitation inherited from the eligible studies, further confirmation in large-scale and well-designed studies is needed.

Association between TP53 gene Arg72Pro polymorphism and idiopathic infertility in southeast Chinese Han males

TP53 is a tumor-suppressor gene which is involved in multiple pathways including apoptosis, transcriptional regulation, and cell cycle control. To analyze whether the TP53 gene Arg72Pro polymorphism (rs1042522) is responsible for susceptibility to idiopathic infertility in southeast Chinese Han males, we used the PCR restriction fragment length polymorphism technique to detect the genotype distribution of 361 infertile men (including 212 with non-obstructive azoospermia and 149 with severe oligozoospermia) in comparison with 384 fertile controls. Genotyping was confirmed by DNA sequencing from randomly selected samples. The frequency of rs1042522 indicated an association with risk of idiopathic male infertility under a dominant mode (GG + GC genotypes vs. CC genotype, P = 0.013; χ2 = 6.169; OR = 1.581; 95%CI = 1.1-2.272; df = 1). Comparison of the allele frequencies revealed a significantly higher incidence of Arg allele among azoospermia group compared with controls (P = 0.001; χ2 =10.864; OR = 1.502; 95%CI = 1.177-1.917; df = 1). Our data suggest that the Arg allele was related only to azoospermia, not to severe oligozoospermia (P = 0.133; χ2 = 2.261; OR = 1.23; 95%CI = 0.939-1.611; df = 1). This study indicated that the TP53 gene Arg72Pro polymorphism of the spermatogenic pathway may be associated with idiopathic infertility in southeast Chinese Han males.

Smoking Status Modifies the Relation Between CYP1A1*2C Gene Polymorphism and Idiopathic Male Infertility: The Importance of Gene–Environment Interaction Analysis for Genetic Studies of the Disease

The study was designed to investigate the associations of polymorphisms Ile462Val and 3801T>C of the cytochrome P450 1A1 (CYP1A1) gene with idiopathic male infertility (IMI) and to assess the impact of smoking status on the relationship between the polymorphisms and the susceptibility to the disease. DNA samples from 203 patients with IMI and 227 fertile men were genotyped for the polymorphisms by a polymerase chain reaction and restriction fragment length polymorphism methods. We found for the first time that the increased risk of IMI in carriers of genotype 462Ile/Val of the CYP1A1 gene occurred only in smoker men (odds ratio [OR] = 1.91; 95% confidence interval [CI] 1.01-3.59), whereas nonsmoker men did not have the risk of infertility (OR = 1.58; 95% CI 0.66-3.76). The results of our study demonstrate that the analysis of gene-environment interactions is necessary to explain conflicting results of genetic studies of IMI and to improve our understanding of the mechanisms of the disease.