Analysis of STAG3 variants in Chinese non-obstructive azoospermia patients with germ cell maturation arrest

AbstractSTAG3 is essential for male meiosis and testis of male Stag3−/− mice shows the histopathological type of germ cell maturation arrest (MA). Whether variants of the STAG3 gene exist in Chinese idiopathic non-obstructive azoospermia (NOA) patients needs to be determined. We recruited 58 Chinese NOA men with MA who underwent testis biopsy and 192 fertile men as the control group. The 34 exons of the STAG3 gene were amplified using polymerase chain reaction (PCR) and sequenced. We identified eight novel single nucleotide polymorphisms (SNPs), including two missense SNPs (c.433T > C in exon2 and c.553A > G in exon3), three synonymous SNPs (c.539G > A, c.569C > T in exon3, and c.1176C > G in exon8), and three SNPs in introns. The allele and genotype frequencies of the novel and other SNPs have no significant differences between two groups. Our results indicated that variants in the coding sequence of the STAG3 gene were uncommon in NOA patients with MA in Chinese population. Future studies in large cohorts of different ethnic populations will be needed to determine the association between the STAG3 gene and NOA.

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Analysis of STAG3 Mutations in Chinese Non-Obstructive Azoospermia Patients with Germ Cell Maturation Arrest

10.21203/rs.3.rs-63652/v1 ◽

2020 ◽

Author(s):

Wen Liu ◽

Xuan Gao ◽

Haobo Zhang ◽

Ran Liu ◽

Yongzhi Cao ◽

...

Keyword(s):

Germ Cell ◽

Male Meiosis ◽

Cell Maturation ◽

Control Group ◽

Obstructive Azoospermia ◽

The Novel ◽

Nucleotide Polymorphisms ◽

Maturation Arrest ◽

Ethnic Populations ◽

Genotype Frequencies

Abstract Background STAG3 is essential for male meiosis and testis of male Stag3-/- mice shows the histopathological type of germ cell maturation arrest (MA). Whether mutations of the STAG3 gene exist in Chinese idiopathic non-obstructive azoospermia (NOA) patients needs to be determined. Methods We recruited 58 Chinese NOA men with MA who underwent testis biopsy and 192 fertile men as the control group. The 34 exons of the STAG3 gene were amplified using polymerase chain reaction (PCR) and sequenced. Results We identified eight novel single nucleotide polymorphisms (SNPs), including two missense SNPs (c.433T>C in exon2 and c.553A>G in exon3), three synonymous SNPs (c.539G>A, c.569C>T in exon3, and c.1176C>G in exon8), and three SNPs in introns. The allele and genotype frequencies of the novel and other SNPs have no significant differences between two groups. Conclusions Our results indicated that mutations in the coding sequence of the STAG3 gene were uncommon in NOA patients with MA in Chinese population. Future studies in large cohorts of different ethnic populations will be needed to determine the association between the STAG3 gene and NOA.

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IL-10-592 A/C Gene Polymorphism and Cytokine Levels are Associated with Susceptibility to Drug Resistance in Tuberculosis

Turkish Journal of Immunology ◽

10.25002/tji.2020.1235 ◽

2020 ◽

Vol 8 (3) ◽

pp. 103-112

Author(s):

Atefeh SADEGHI SHERMEH ◽

Majid KHOSHMIRSAFA ◽

Ali-Akbar DELBANDI ◽

Payam TABARSI ◽

Esmaeil MORTAZ ◽

...

Keyword(s):

Serum Levels ◽

World Health ◽

Control Group ◽

Drug Resistant ◽

Nucleotide Polymorphisms ◽

Genotype Frequencies ◽

Cytokine Levels ◽

Ifn Γ ◽

Health Organization ◽

And Function

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis

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BAX gene (−248 G > A) polymorphism in a sample of patients diagnosed with thyroid cancer in the Federal District, Brazil

The International Journal of Biological Markers ◽

10.1177/17246008211057576 ◽

2021 ◽

pp. 172460082110575

Author(s):

Ligia C.A. Cardoso-Duarte ◽

Caroline F. Fratelli ◽

Alexandre S.R. Pereira ◽

Jéssica Nayane Gomes de Souza ◽

Renata de Souza Freitas ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Protective Factor ◽

Federal District ◽

Genotypic Difference ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Papillary Thyroid ◽

Genotype Frequencies ◽

Bax Gene

Introduction Papillary thyroid cancer corresponds to approximately 1% of all carcinomas; nevertheless, it is the most prevalent endocrine neoplasm in the world. Studies reveal that the BAX (−248 G > A) polymorphism may be associated with negative regulation of BAX gene transcription activity, causing a decrease in its protein expression. Objective The present study aimed to describe the genotype and allele frequencies of BAX single nucleotide polymorphisms (−248 G > A) (rs4645878) in the research patients, and to associate its presence with susceptibility to papillary thyroid cancer. Methods This case-control study was conducted with 30 patients with papillary thyroid cancer. For the evaluation of genetic polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism technique was employed. Allele and genotype frequencies were estimated using the SPSS program, and significant associations were considered when p < 0.05. Results There was a significant genotypic difference between papillary thyroid cancer and the control group (p = 0.042). The GG genotype provided a protective factor for papillary thyroid cancer (p = 0.012, odds ratio (OR) = 0.313; confidence interval (CI) = 0.123–0.794). Likewise the G allele was a protective factor for papillary thyroid cancer (p = 0.009; OR = 0.360; CI = 0.163–0.793). The BAX gene polymorphism (−248 G > A) was associated with papillary thyroid cancer. Conclusion BAX (−248 G > A) GG genotype carriers, or at least one mutated allele, was associated with papillary thyroid cancer in the Brazilian population studied, and the G allele presence is considered a protective factor against papillary thyroid cancer occurrence.

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The association of FKBP5 polymorphism with asthma susceptibility in asthmatic patients

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0450 ◽

2021 ◽

Vol 32 (4) ◽

pp. 479-484

Author(s):

Sura F. Alsaffar ◽

Haider A. Rasheed ◽

Jabbar H. Yenzeel ◽

Haider F. Ghazi

Keyword(s):

Allele Frequency ◽

Risk Allele ◽

Inhaled Corticosteroids ◽

Control Group ◽

The Novel ◽

Nucleotide Polymorphisms ◽

Asthmatic Patients ◽

Asthma Susceptibility ◽

Group Members ◽

Novel Snp

Abstract Objectives Inhaled corticosteroids are the most effective controllers of asthma, although asthmatics vary in their response. FKBP51 is a major component of the glucocorticoid receptor which regulates its responses to corticosteroids. Therefore, the present study aims to identify the role of FKBP5 gene polymorphism in asthma susceptibility and corticosteroid resistance. Methods DNA was extracted from the blood of 68 asthmatic and 40 control subjects. FKBP5 gene fragments were amplified by PCR and sequenced by the Sanger method. The sequencing results were aligned by mapping on the reference sequences of National center of Biotechnology Information (NCBI) and single nucleotide polymorphisms (SNPs) which were checked. Finally, the genotype, allele frequency and odds ratio (OR) were calculated. Results The FKBP5 fragment sequencing revealed the presence of rs1360780 and one novel SNP found in 17 samples taken from asthmatic patients as compared to db SNP data in the NCBI database. The FKBP5 variant (rs1360780) indicated that the allele frequency of risk allele T was 41.18% in patients and 20% in control group members p<0.001 and OR=2.8 when compared to a wild C allele frequency of 58.82% in patients and 64% in the control group members. The novel SNP FKBP5 was compared to the SNP database in the NCBI database in which wild T allele was substituted with G. The novel SNP was submitted to the ClinVar Submission Portal at NCBI with accession number: rs1581842283 and confirmed an asthma susceptibility risk factor with allele G frequency of 11.76% in asthmatics and 2.5% in the control group members (OR=5.2, p<0.05), as compared to a wild T allele frequency of 88.24% in asthmatics and 97.5% in the control group members. Conclusions The risk allele T of rs1360780 and the novel SNP rs1581842283 risk allele G predict asthma susceptibility but show no association with corticosteroid resistant.

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A Study of IL-1β, MMP-3, TGF-β1, and GDF5 Polymorphisms and Their Association with Primary Frozen Shoulder in a Chinese Han Population

BioMed Research International ◽

10.1155/2017/3681645 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Wenxiang Chen ◽

Jia Meng ◽

Hong Qian ◽

Zhantao Deng ◽

Shuo Chen ◽

...

Keyword(s):

Inflammatory Diseases ◽

Frozen Shoulder ◽

Chinese Han Population ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Serum Samples ◽

Chinese Han ◽

Han Population ◽

Genotype Frequencies ◽

Uncertain Etiology

Primary frozen shoulder (PFS) is a common condition of uncertain etiology that is characterized by shoulder pain and restriction of active and passive glenohumeral motions. The pathophysiology involves chronic inflammation and fibrosis of the joint capsule. Single nucleotide polymorphisms (SNPs) at IL-1β, MMP3, TGF-β1, and GDF5 have been associated with risk of a variety of inflammatory diseases; however, no studies have examined these SNPs with susceptibility to PFS. We investigated allele and genotype frequencies of rs1143627 at IL-1β, rs650108 at MMP-3, rs1800469 at TGF-β1, and rs143383 at GDF5 in 42 patients with PFS and 50 healthy controls in a Chinese Han population. Serum samples from both cohorts were evaluated to determine the expression levels of IL-1β. We found that the IL-1β rs1143627 CC genotype was associated with a decreased risk of PFS compared to the TT genotype (P=0.022) and that serum IL-1β was expressed at a significantly higher level in the PFS cohort compared to that found in the control group (P<0.001). Our findings indicated no evidence of an association between rs650108, rs1800469, or rs143383 and PFS. IL-1β is associated with susceptibility to PFS and may have a role in its pathogenesis in a Chinese Han population.

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NOTCH4 Single-Nucleotide Polymorphism Is Associated With Brain Arteriovenous Malformation in a Chinese Han Population

10.21203/rs.3.rs-1101933/v1 ◽

2021 ◽

Author(s):

Jianbo Zhang ◽

Zhenjun Li ◽

Haiyan Fan ◽

Hengxian Su ◽

Hongliang Meng ◽

...

Keyword(s):

Arteriovenous Malformation ◽

Gene Polymorphisms ◽

Vascular Malformations ◽

Chinese Han Population ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population ◽

Genotype Frequencies

Abstract Background: Brain arteriovenous malformations (BAVMs) are high-flow intracranial vascular malformations characterized by the direct connection of arteries to veins without an intervening capillary bed. It is one of the main causes of intracranial hemorrhage and epilepsy though morbidity is low. Angiogenesis, heredity, inflammation, and arteriovenous malformation syndromes play important roles in BAVM formation. Animal experiments and previous studies have confirmed that NOTCH4 may be associated with BAVM development. Our study identifies a connection between NOTCH4 gene polymorphisms and BAVM in a Chinese Han population.Methods: We enrolled 150 patients with BAVMs confirmed by digital subtraction angiography (DSA) in the Department of Neurosurgery, Zhujiang Hospital, Southern Medical University from June 2017 to July 2019. Simultaneously, 150 patients without cerebrovascular disease were confirmed by computed tomography angiography/magnetic resonance angiography/DSA. DNA was extracted from peripheral blood and NOTCH4 genotypes were identified by PCR-ligase detection reaction. Chi-square test or Fisher’s exact test was used to evaluate the difference in allele and genotype frequencies between the BAVM group, control group, bleeding, and other complications.Results: Two single-nucleotide polymorphisms (SNPs), rs443198 and rs438475, were significantly associated with BAVM. No SNP genotypes were significantly associated with hemorrhage and epilepsy. SNPs rs443198_ AA-SNP and rs438475_ AA-SNP may be associated with lower risk of BAVM (P = 0.011, OR = 0.459, 95% CI 0.250–0.845; P = 0.033, OR = 0.759, 95% CI 0.479–1.204).Conclusion: NOTCH4 gene polymorphisms were associated with BAVM and may be a risk factor in a Chinese Han population.

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FASandFASLGene Polymorphisms Are Not Associated with Hepatitis B Virus Infection Based on a Case-Control Study in a Brazilian Population

Disease Markers ◽

10.1155/2013/964145 ◽

2013 ◽

Vol 35 ◽

pp. 741-746 ◽

Cited By ~ 3

Author(s):

Bárbara B. Santana ◽

Maria Luana C. Viégas ◽

Simone R. S. S. Conde ◽

Marluísa O. G. Ishak ◽

Ricardo Ishak ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Control Group ◽

Active Chronic Hepatitis ◽

Nucleotide Polymorphisms ◽

Genotype Frequencies ◽

Brazilian Amazon Region ◽

B Virus

Objective. This study investigated the association of the single nucleotide polymorphisms (SNPs) in theFASandFASLgenes with the outcome of hepatitis B virus (HBV) infection.Methods. Blood samples were collected from 116 HBV-infected patients at the Hospital of the Santa Casa de Misericordia Foundation (Belém, PA, Brazil). Seronegative individuals were used as controls. DNA samples were extracted from the leukocytes and assayed using the polymerase chain reaction (PCR) followed by RFLP analysis with restriction endonucleases.Results. The frequencies of the mutant genotypes for -670FAS(GG), Ivs2nt-124FASL(GG), Ivs3nt-169FASL(ΔT/ΔT), and -844FASL(TT) were higher in the HBV patients, and theFAS-1377AA genotype was more frequent in the control group; however, the differences between the allele and genotype frequencies were not statistically significant. When the HBV patient population was divided into two groups (inactive carriers and active chronic hepatitis patients), the mutant genotypes were found to be more prevalent in the active chronic hepatitis group with respect to theFASgene polymorphisms; however, this difference was not statistically significant.Conclusions. The results suggest that the polymorphisms inFASandFASLgenes are not associated with HBV infection or even with the natural history of the infection in the Brazilian Amazon region.

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Association of PIWIL4 genetic variants with germ cell maturation arrest in infertile Spanish men

Asian Journal of Andrology ◽

10.4103/1008-682x.131069 ◽

2014 ◽

Vol 16 (6) ◽

pp. 931 ◽

Cited By ~ 5

Author(s):

Sara Larriba ◽

Xavi Muñoz ◽

Mercedes Navarro ◽

Ana Mata ◽

Lluís Bassas

Keyword(s):

Germ Cell ◽

Genetic Variants ◽

Cell Maturation ◽

Maturation Arrest

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Association of LAG3 genetic variation with an increased risk of PD in Chinese female population

Journal of Neuroinflammation ◽

10.1186/s12974-019-1654-6 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 2

Author(s):

Wenyuan Guo ◽

Miaomiao Zhou ◽

Jiewen Qiu ◽

Yuwan Lin ◽

Xiang Chen ◽

...

Keyword(s):

Lymphocyte Activation ◽

Control Group ◽

Strong Linkage Disequilibrium ◽

Nucleotide Polymorphisms ◽

Serum Samples ◽

Meso Scale Discovery ◽

Female Population ◽

Genotype Frequencies ◽

Potential Biomarker ◽

Increased Risk

Abstract Background Emerging evidence suggests that α-synuclein (α-syn) aggregation and intercellular transmission contributes to pathogenesis of Parkinson’s disease (PD) and the toxic fibrillary α-syn binds lymphocyte-activation gene 3 (LAG3) receptor that mediates α-syn transmission. The deletion of LAG3 in animal models was shown to limit α-syn spreading and alleviate the pathological changes of dopaminergic neurons and animal behavioral deficits induced by α-syn aggregation. However, little is known about the genetic association of LAG3 variation with human PD development. Objective Here we investigated LAG3 single nucleotide polymorphisms (SNPs) and examined the levels of soluble LAG3 (sLAG3) of CSF and serum from Chinese PD patients. Methods We enrolled 646 PD patients and 536 healthy controls to conduct a case-control study. All the participants were genotyped using Sequenom iPLEX Assay and the partial cerebrospinal fluid (CSF) and serum samples were assessed by Meso Scale Discovery electrochemiluminescence (MSD-ECL) immunoassay to measure sLAG3 concentration. Results As a result, distributions of rs1922452-AA (1.975, 95% confidence interval (CI) 1.311–2.888, p = 0.001) and rs951818-CC (OR = 2.03, 95% CI 1.369–3.010, p = 0.001) genotype frequencies were found higher in the female PD patients than controls, respectively, and a strong linkage disequilibrium (LD) was calculated on the variants. The level of sLAG3 in CSF of PD patients was found to significantly differ from that of controls (51.56 ± 15.05 pg/ml vs 88.49 ± 62.96 pg/ml, p < 0.0001). Meanwhile, the concentration of α-synuclein in CSF of patients was significantly lower than that of controls (939.9 ± 2900 pg/ml vs 2476 ± 4403 pg/ml, p < 0.0001) and the level of sLAG3 was detected to be positive correlation with that of α-synuclein in the control group (r = 0.597, p = 0.0042), but not in PD group (r = 0.111, p = 0.408). Conclusion In summary, our data suggested that LAG3 SNPs increase the PD risk of Chinese female population and the sLAG3 may be a potential biomarker predicted for PD development.

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Mitochondrial nicotinamide adenine dinucleotide hydride dehydrogenase (NADH) subunit 4 (MTND4) polymorphisms and their association with male infertility

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-021-02199-w ◽

2021 ◽

Author(s):

Fatina W. Dahadhah ◽

Mayyas Saleh Jaweesh ◽

Mazhar Salim Al Zoubi ◽

Manal Issam Abu Alarjah ◽

Mohamad Eid Hammadeh ◽

...

Keyword(s):

Mitochondrial Dna ◽

Male Infertility ◽

Semen Analysis ◽

Control Group ◽

Case Group ◽

Nucleotide Polymorphisms ◽

Genotype Frequencies ◽

Study Population ◽

The Relationship ◽

Sanger Method

Abstract Purpose The purpose of the present study was to determine the relationship between infertility and the polymorphisms of mitochondrial NADH dehydrogenase subunit 4 (MTND4) by spermatozoa analysis in fertile and subfertile men. Methods Samples were divided into 68 subfertile men (case group) and 44 fertile men (control group). After semen analysis, samples were purified. The whole genome was extracted using a QIAamp DNA Mini Kit and the mitochondrial DNA was amplified by using the REPLI-g Mitochondrial DNA Kit. Polymerase chain reaction (PCR) was used to amplify the MT-ND4 gene. Then, samples were purified and sequenced using the Sanger method. Results Twenty-five single-nucleotide polymorphisms (SNPs) were identified in the MTND4 gene. The genotype frequencies of the study population showed a statistically significant association between rs2853495 G>A (Gly320Gly) and male infertility (P = 0.0351). Similarly, the allele frequency test showed that rs2853495 G>A (Gly320Gly) and rs869096886 A>G (Leu164Leu) were significantly associated with male infertility (adjusted OR = 2.616, 95% CI = 1.374–4.983, P = 0.002; adjusted OR = 2.237, 95% CI = 1.245–4.017, P = 0.007, respectively). Conclusion In conclusion, our findings suggested that male infertility was correlated with rs2853495 and rs869096886 SNPs in MTND4.

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