BackgroundMale infertility is a complex disorder caused by genetic, developmental, endocrine, or environmental factors as well as unknown etiology. Polymorphisms in the follicle stimulating hormone beta subunit (FSHB) (rs10835638, c.-211G > T) and follicle stimulating hormone receptor (FSHR) (rs1394205, c.-29G > A; rs6165, c.919A > G; rs6166, c.2039 A > G) genes might disturb normal spermatogenesis and affect male reproductive ability.MethodsTo further ascertain the aforementioned effects, we conducted a case-control study of 255 infertile men and 340 fertile controls from South China using the Mass ARRAY method, which was analyzed by the t-tests and logistic regression analysis using SPSS for Windows 14.0. In addition, a meta-analysis was performed by combining our results with previous reports using STATA 12.0.ResultsIn the FSHB or FSHR gene single nucleotide polymorphism (SNP) evaluation, no statistically-significant difference was found in the frequency of allelic variants or in genotype distribution between cases and controls. However, a significant association for the comparison of GAA (P: 0.022, OR: 0.63, 95%CI: 0.43–0.94) was seen between the oligozoospermia and controls in haplotype analysis of rs1394205/rs6165/rs6166. In the meta-analysis, rs6165G allele and rs6166 GG genotype were associated with increased risk of the male infertility.ConclusionsThis study suggested that FSHR GAA haplotype would exert protective effects against male sterility, which indicated that the combination of three SNP genotypes of FSHR was predicted to have a much stronger impact than either one alone. Then in the meta-analysis, a significant association was seen between FSHR rs6165, rs6166 polymorphisms and male infertility. In terms of male infertility with multifactorial etiology, further studies with larger sample sizes and different ethnic backgrounds or other risk factors are warranted to clarify the potential role of FSHB and FSHR polymorphisms in the pathogenesis of male infertility.
Dear Editor, Coronavirus disease 2019 (COVID-19) has infected tens of millions of people worldwide since its pandemic. 1 No specific therapeutic agents or vaccines for COVID-19 are available. Convalescent plasma refers to plasma separated from an individual after the infection has subsided and the antibody has developed. 2-5 Convalescent plasma therapy (CPT), a classic adaptive immunotherapy, has been successfully used for the prevention and treatment of many infectious diseases for more than one century. Over the past two decades, it was successfully used in the treatment of severe acute respiratory syndrome (SARS) in 2003, H1N1 influenza pandemic in 2009, and Middle East Respiratory Syndrome (MERS) from 2012 to 2017 with satisfactory efficacy and safety. CPT is one of the promising treatment methods and is favored by more and more researchers. 2-10 However, the clinical efficacy and safety of CPT in COVID-19 remains unclear. We performed a retrospective observational study by propensity score matching analysis (PSM) and metaanalysis estimates the clinical efficacy and security of CPT and COVID-19, which will help inform clinical management of COVID-19 infection. A total of 326 participants (163 cases group with CPT and 163 matched controls group with the standard treatment) diagnosed as COVID-19 were included in the clinical study, of which 142 patients (43.56%) were male. The mean age for all patients was 64.07 ± 13.37 years, and the majority (65.64%) of them was more than 60 years old. Of all patients, 79 (48.47%) cases and 77 (47.24%) controls had a history of basic diseases, including hyperlipidemia, diabetes mellitus, coronary heart disease, and tumor. Interestingly, we found that days of hospital stay in case with CPT groups were significantly higher than matched control group (P < 0.0001). Possible explanation is that most of patients in the CPT treatment group condition This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The antioxidant defense system protects DNA from the damaging effects of oxidative stress and is hypothesized to be associated with an increased risk of male infertility. Polymorphisms in antioxidant genes and the gene-gene interactions associated with the antioxidant system may increase the potential risk of male infertility. In the present case-controlled study, the individual link between seven gene polymorphisms (NQO1 rs1800566, SOD2 rs4880, GSTM3 rs1571858, rs3814309, rs7483, GSTM5 rs11807 and GSTP1 rs1695) and the risk of male infertility was investigated. A total of 248 idiopathic infertility patients and 310 fertile controls were selected, and genotyping was performed using the Mass ARRAY platform. There were no significant associations between the seven polymorphisms and risk of male infertility. However, the analysis of gene-gene interactions showed a decreased risk of male infertility in GSTM3 rs3814309/NQO1 rs1800566 [CC x CT/TT; odds ratio (OR)=0.56, 95% confidence interval (CI)=0.34-0.92; P=0.022), and a significant association between a gene-gene interaction in GSTM3 rs1571858/NQO1 rs1800566 and azoospermia (AG/GG x CC; OR=3.84, 95% CI=1.25-11.81; P=0.019).
Protamine (PRM) plays important roles in the packaging of DNA within the sperm nucleus. To investigate the role of PRM1/2 and transition protein 1 (TNP1) polymorphisms in male infertility, 636 infertile men and 442 healthy individuals were recruited into this case-controlled study of the Chinese Han population, using MassARRAY technology to analyze genotypes. Our analysis showed that there were no significant differences between controls and infertile cases among the five single nucleotide polymorphisms identified in PRM1, PRM2 and TNP1 [rs737008 (G/A), rs2301365 (C/A), rs2070923 (C/A), rs1646022 (C/G) and rs62180545 (A/G)]. However, we found that the PRM1 and PRM2 haplotypes GCTGC, TCGCA and TCGCC exhibited significant protective effects against male infertility compared to fertile men, while TCGGA, GCTCC and TCGGC represented significant risk factors for spermatogenesis. Our data showed that rs737008 and rs2301365 in PRM1, and rs1646022 in PRM2, were significantly associated with male infertility and that gene–gene interaction played a role in male infertility. A linkage disequilibrium plot for the five SNPs showed that rs737008 was strongly linked with both rs2301365 and rs2070923. These findings are likely to help improve our understanding of the etiology of male infertility. Further studies should include a larger number of genes and SNPs, particularly growing critical genes; such studies will help us to unravel the effect of individual genetic factors upon male infertility.
The risk of testicular cancer (TC) is markedly increased in subjects with androgen insensitivity, and previous studies have proposed that GGN and CAG repeats in androgen receptors (AR) could be related to the risk of TC. To evaluate the association between the length of GGN and CAG repeats in AR and TC, a meta-analysis involving 3255 TC cases and 2804 controls was performed. The results suggested that long GGN repeats are associated with an increased risk of TC compared with those < 23 [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.05–1.41]; similarly, a subgroup analysis revealed that this association occurred in studies with case sizes > 200, and in the mid-latitude, and seminoma subgroups. The subgroup analysis based on populations, high-latitude, and seminomas/non-seminomas suggested that AR CAG repeat polymorphisms with > 25 and < 21 + > 25 repeats might confer a protective effect to the patients with TC (in the high-latitude subgroup analysis, for > 25 vs. 21–25: OR = 0.54, 95% CI = 0.41–0.70). In contrast, an increased risk of TC was observed for AR CAG repeat polymorphisms with > 25 and < 21 + > 25 repeats in the mid-latitude subgroup (for > 25 vs. 21–25: OR = 1.65, 95% CI = 1.09–2.50). In addition, no associations between the remaining subgroups and male infertility were observed. In short, this meta-analysis suggested that AR GGN and CAG repeat polymorphisms may be involved in the etiology of TC.
Objectives: With the worldwide spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), various antibody detection kits have been developed to test for SARS-CoV-2– specific IgG, IgM, and total antibody. However, the use of different testing methods under various heat-inactivation conditions might affect the COVID-19 detection results.Methods: Seven different antibody detection kits produced by four manufacturers for detection of SARS-CoV-2 IgG, IgM, and total antibody were tested at Wuhan Huoshenshan Hospital, China. Most of the kits used the indirect immunity, capture, and double-antigen sandwich methods. The effects of various heat-inactivation conditions on SARS-CoV-2-specific IgG, IgM, and total antibody detection were analyzed for the different test methods.Results: Using the indirect immunity method, values for SARS-CoV-2 IgG antibody significantly increased and those for IgM antibody decreased with increasing temperature of heat-inactivation using indirect immunity method. However, values for SARS-CoV-2 IgM and total antibody showed no change when the capture and double-antigen sandwich methods were used. The changes in IgG and IgM antibody values with the indirect immunity method indicated that heat-inactivation could affect COVID-19 detection results obtained using this method. In particular, 18 (22.2%) SARS-CoV-2 IgM positive samples were detected as negative with heat-inactivation at 65°C for 30 min, and one (25%) IgG negative sample was detected as positive after heat-inactivation at 56°C for 60 min and 60°C for 30 min.Conclusions: Heat-inactivation could increase SARS-CoV-2 IgG antibody values, and decrease IgM antibody values, causing potential false-positive or false-negative results for COVID-19 antibody detection using the indirect immunity method. Thus, before conducting antibody testing, the testing platforms should be evaluated in accordance with the relevant requirements to ensure accurate COVID-19 detection results.
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