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ABSTRACT This study aims to investigate the association of rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 polymorphisms of protein‐arginine deiminase type 4 (PADI4) gene with the risk of rheumatoid arthritis (RA) through a meta‐analysis that was followed with a bioinformatics approach. The data were collected from reputable articles and underwent quantitative analysis, followed by in silico analysis using some bioinformatics tools. The results showed that rs874881 polymorphism in Latino (G vs. C: OR = 1.35, 95% CI = 1.11–1.65, p = 0.003; GG + CG vs. CC: OR = 2.02, 95% CI = 1.41–2.89, p = 0.0001; CG vs. CC + GG: OR = 1.38, 95% CI = 1.04–1.83, p = 0.027; GG vs. CC: OR = 2.09, 95% CI = 1.35–3.23, p = 0.001; CG vs. CC: OR = 1.98, 95% CI = 1.36–2.87, p = 0.00033) and rs1748033 in Caucasian population (T vs. C: OR = 1.25, 95% CI = 1.07–1.45, p = 0.005; TT vs. CT + CC: OR = 1.34, 95% CI = 1.09–1.64, p = 0.005, TT + CT vs. CC: OR = 1.26, 95% CI = 1.09–1.44, p = 0.001; TT vs. CC: OR = 1.59, 95% CI = 1.13–2.23, p = 0.007; CT vs. CC: OR = 1.20, 95% CI: 1.04–1.39, p = 0.015) are associated with increased risk of RA. Moreover, rs11203366 (G vs. A: OR = 1.46, 95% CI = 1.19–1.78, p = 0.0002, GG vs. AG + AA: OR = 1.42, 95% CI = 1.01–2.01, p = 0.043; GG + AG vs. AA: OR = 2.03, 95% CI = 1.45–2.86, p = 0.00004; GG vs. AA: OR = 2.29, 95% CI = 1.49–3.51, p = 0.0002; AG vs. AA: OR = 1.93, 95% CI = 1.35–2.76, p = 0.0003) and rs11203367 (T vs. C: OR = 1.50, 95% CI = 1.23–1.83, p = 0.00007; TT vs. CT + CC: OR = 1.56, 95% CI = 1.12–2.18, p = 0.009; TT + CT vs. CC: OR = 2.02, 95% CI = 1.43–2.84, p = 0.00007, TT vs. CC: OR = 2.43, 95% CI = 1.59–3.71, p = 0.0004; CT vs. CC: OR = 1.86, 95% CI = 1.30–2.68, p = 0.0007) had an impact in the Latino population. Bioinformatics tools showed the effect of these polymorphisms on gene function. These findings suggest that rs11203366, rs11203367, rs874881 and rs1748033 polymorphisms may be genetic risk factors for RA. Moreover, differences between populations suggest that ethnicity may play an important role in the effect of these polymorphisms on RA risk. [ABSTRACT FROM AUTHOR]

Aim: CYP1A1 is a metabolizing enzyme and key polymorphisms in its gene may contribute to the risk of ischemic stroke. This study aimed to investigate the association of the rs4646903 and rs1048943 polymorphisms of CYP1A1 with stroke risk in a meta-analysis and a bioinformatic approach. Materials & methods: An electronic search was conducted and, after the screening procedure, six eligible studies were included in the meta-analysis. Some bioinformatic tools were employed to analyze the effects of rs4646903 and rs1048943 on CYP1A1 gene function. Results: There was a significant association between rs4646903 and the reduced risk of ischemic stroke, whereas there was no significant association for rs1048943. In silico analysis showed that rs4646903 and rs1048943 polymorphisms could affect the gene expression and cofactor affinity, respectively. Conclusion: Based on these results, rs4646903 may be a protective genetic factor against ischemic stroke. [ABSTRACT FROM AUTHOR]

Paraoxonase 1 (PON1), an enzyme with multifactorial antioxidant activity, has a protective role against oxidative stress, which is supposed to contribute to the development of cancers including breast cancer. The aim of this study was to examine the correlation of PON1-L55M common genetic polymorphism with the risk of breast cancer in a meta-analysis approach which was followed by an in silico analysis. The eligible studies were collected from valid electronic databases such as Google Scholar, PubMed, Embase, and Web of Science. Quantitative synthesis was performed to report the strength of PON1-L55M polymorphism with breast cancer. Some bioinformatics tools were used to analyze the effects of L55M variation on PON1 gene function. The meta-analysis revealed that there are significant associations between the mentioned polymorphism and breast cancer in M vs. L, MM vs. LL, LM vs. LL, MM + LM vs. LL, and MM vs. LL + LM genetic models. Besides, similar results were observed in the stratified analyses based on ethnicity, genotyping method, Hardy-Weinberg equilibrium in control groups, and sample size. Bioinformatics analysis revealed that the PON1 could be damaging to the protein function. Our findings propose that the PON1-L55M genetic polymorphism might be a genetic risk factor for the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE), a multifactorial disorder, is the main cause of maternal mortality and morbidity. Genetic polymorphisms in key proteins involved in the immune system may change the risk of PE risk. In this study, we examined the association of two rs2232365 and rs3761548 common polymorphisms of the FOXP3 immune response gene with PE susceptibility by a meta-analysis which was followed by an in-silico analysis. Through a systematic search in databases including PubMed, MEDLINE, Google Scholar, and Science Direct, we find eligible studies for meta-analysis. Some bioinformatics tools were used to detect the impact of rs2232365 and rs3761548 polymorphisms on the FOXP3 gene function. Our data revealed that there is a significant association between rs3761548 polymorphism and decreased risk of PE. In addition, we observed a significant association between rs2232365 and increased risk of mild preeclampsia. Also, our bioinformatic analysis showed that both rs2232365 and rs3761548 polymorphisms could affect FOXP3 gene function. Based on our findings, the rs3761548 genetic variation could be a protective factor against PE risk. While the rs2232365 polymorphism may be a genetic risk factor for mild preeclampsia. Therefore, as a preliminary study, these genetic variations could be considered molecular biomarkers for PE disorder. [ABSTRACT FROM AUTHOR]

Vitamin and homocysteine (Hcy) alternations have been associated with psychiatric disorders. The aim of this meta-analysis was to assess the association of serum vitamin and Hcy levels with obsessive-compulsive disorder (OCD). Following PRISMA protocol, we used the databases including Scopus, PubMed, Google Scholar, and Web of Science with no time restriction. Data were pooled using a random-effects model and/or fixed-effects model to estimate the standard mean difference (SMD) for evaluation of the strength of association analyses. Our data showed a significant reduction in vitamin B12 (SMD = −0.58, 95% CI = −1.08 to −0.08, p = 0.02, I2 = 65%; pheterogeneity = 0.06), vitamin E (SMD = −0.89, 95% CI = −1.23 to −0.56, p < 0.00001, I2 = 23%; pheterogeneity = 0.26), and vitamin C (SMD = −1.40, 95% CI = −2.44 to −0.36, p = 0.008, I2 = 92%; pheterogeneity < 0.0001) in OCD patients. In addition, the findings showed significantly higher levels of Hcy (SMD = 1.11, 95% CI = [0.48, 1.75], p = 0.0006, I2 = 73%; ph = 0.02) in patients compared to controls. Also, our data showed that vitamin B9 and D levels are not associated with OCD (vitamin B9: SMD = −0.23, 95% CI = −1.01 to 0.55, p = 0.56, I2 = 88%; pheterogeneity < 0.0001; vitamin D: SMD = −0.63, 95% CI = −1.41 to 0.15, p = 0.11, I2 = 88%; pheterogeneity = 0.0002). Our findings support significant impacts of Hcy and vitamin B12, E, and C levels in OCD pathogenesis. This will be important for prevention and treatment of OCD. However, further studies are recommended to elucidate more accurate conclusions. [ABSTRACT FROM AUTHOR]

Chronic periodontitis (CP) is a common inflammatory disorder with a considerable impact of genetic variations in the interleukin family on predisposition to this disease. This study aimed to investigate the association between the -592C>A polymorphism of the interleukin 10 (IL-10) gene with CP risk in an Iranian population. This experimental study was followed by a meta-analysis and in silico examination. In a case-control study, 270 subjects, including 135 patients with CP and 135 healthy controls, were enrolled. The -592C>A genotyping was performed using the PCR-RFLP method. In the meta-analysis, valid databases were systematically searched to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed to examine the association between -592C>A and CP. In silico analysis was conducted using bioinformatics tools to evaluate the impact of the -592C>A polymorphism on IL-10 gene function. Our case-control study revealed a significant association between polymorphism and CP risk. Overall, we found significant associations between -592C>A genetic variation and CP and stratified meta-analysis. In silico analysis revealed that this polymorphism could change the pattern of the transcription binding site upstream of the IL-10 gene. It may also alter the hsa-miR-101-3p miRNA-targeted sequence upstream of IL-10. Based on our results, the -592C>A variation in IL-10 may be a genetic risk factor for susceptibility to chronic periodontitis. However, further studies in different ethnicities and results adjusted for clinical and demographic characteristics are needed to obtain more accurate deductions. • The -592C>A genetic polymorphism is associated with chronic periodontitis in Iranian population. • The -592C>A genetic polymorphism is a risk factor for chronic periodontitis in Asian population. • The -592C>A genetic variation may alter IL-10 gene expression. [ABSTRACT FROM AUTHOR]

Background: Dyspepsia is a highly prevalent gastrointestinal problem. The present study was carried out to assess the prevalence of dyspepsia in Iran. Methods: The present study was registered at PROSPERO with the code CRD42019148610. It was carried out based on MOOSE and reporting was performed according to the PRISMA protocol. Systematic search of the literature was performed in July 2019 on international databases of PubMed/Medline, Web of Science (ISI), Cochrane Library, EBSCO, CINAHL, EMBASE, Scopus, Science Direct, and local databases as well as the Google Scholar search engine. Heterogeneity was evaluated using I² and Chi-square tests. All analyses were done using Comprehensive Meta-Analysis software. Results: Overall, 14 studies with a sample size of 54,118 subjects entered in this meta-analysis. The prevalence of dyspepsia in Iran was 14.6% (95% CI: 9.6-21.7). Large heterogeneity was detected among studies (I² = 99.62%, P < 0.001). The prevalence of dysmotility-like, ulcer-like, and unspecified dyspepsia was estimated to be 9.7% (95% CI: 4.9-18.4), 12.1% (95% CI: 5.2-25.7) and 17.0% (95% CI: 7.8-33.4), respectively. The prevalence of dyspepsia in Iranian men and women was found at 11.1% (95% CI: 6.3-18.8) and 17.8% (95% CI: 10.0-29.7), respectively. Conclusions: The prevalence of dyspepsia in Iran is relatively high. However, it is lower than global estimates. [ABSTRACT FROM AUTHOR]

Several complex rearrangements such as deletions in mitochondrial DNA (mtDNA) have been identified in sperm deficiencies. This study aimed to investigate the association of common mtDNA deletions with male infertility using a meta-analysis approach. Standard databases were systematically searched to discover relevant studies. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI) were estimated to analyze the association of mtDNA deletions with male infertility. Our data revealed a significant association between a common 4977-bp deletion and an increased risk of male infertility. A similar association was observed in an Asian population. Stratified analysis by infertility phenotype showed significant associations between the 4977-bp deletion and increased risk of asthenozoospermia, oligoasthenoteratozoospermia, and asthenoteratozoospermia. In addition, significant associations were found in studies with sample sizes >100, age of participants <45 years, subject selection according to WHO criteria, and studies of moderate to high quality. Regarding the other common mtDNA deletions, significant associations were observed between 7436-bp, 7599-bp, and 4866-bp deletions and the risk of male infertility. Our findings suggest that the 4977-bp deletion might be a risk factor for male infertility, especially in an ethnic and infertility phenotype dependent manner. [ABSTRACT FROM AUTHOR]

Background: Considering the prevalence of COVID-19 worldwide, the present study aimed to determine the prevalence of gastrointestinal problems (anorexia, diarrhea, nausea, and vomiting) in patients with COVID-19. Materials and Methods: The purpose of this study was to determine the prevalence of gastrointestinal problems in patients with COVID-19 using Systematic Review and Meta-analysis methodology. The search was conducted independently by two researchers on international databases, including Web of Science (ISI), Scopus, Embase, Science Direct, PubMed/Medline, and Google Scholar Search Engine. Keywords included “Vomiting”, “Anorexia”, “Diarrhea”, “Nausea”, “SARS-CoV-2”, and “COVID-19”. Data were analyzed using STATA statistic software. Results: The total sample size was 3602 patients. Initially, 1456 studies were included in the study, which reached 33 articles after the final screening. Regarding the prevalence of gastrointestinal problems in patients, the prevalence rate of diarrhea was 6% (95% CI: 0.06 [0.04, 0.08]), anorexia was13% (95% CI: 0.13 [0.03, 0.24]), nausea and vomiting was 4% (95% CI : 0.04 [0.03, 0.05]), and pharyngalgia was 16% (95% CI : 0.16 [0.02, 0.30]). Conclusion: The results of this study can be used as a guideline for clinical professionals. [ABSTRACT FROM AUTHOR]

Background and Objectives: Pain assessment is very important in these patients, but no comprehensive systematic reviews/meta-analyses (SRs/MAs) have been performed so far. For this reason, this study was performed to determine the prevalence of pain in patients with Covid-19 in the world by SR/MA method. Methodology: The researchers collected English language articles in which COVID-19 was confirmed and all SRs/MAs and case reports articles were excluded. Search was carried on at SCOPUS®, PubMed®/MEDLINE®, Web of Science®, Science Direct® and Google Scholar's search engine. To extract the data the checklist contained general information about articles, e.g. authors' names, year of publication, number of patients, country, journal's name, and specific information, e.g. prevalence and percentage of 'sore throat', 'abdominal pain', 'chest pain', 'headache' and 'myalgia'. Results: According to the findings, 326 articles were extracted in the initial search, 218 articles of these were classified as duplicate articles because of the frequency in their authors, magazines and sample size, and were excluded. Also, by reviewing the title, abstract and complete files of articles, 73 articles were excluded as being non-relevant. Out of 35 remaining articles 2 were SRs/MAs in the field of COVID-19 by Iranian authors, and were also excluded. In the remaining 33 articles included in this SR/MA study, the sample size was 3781 patients. Regarding the prevalence of pain in patients, prevalence rate of abdominal pain was 0.02% (95% CI: 0.01, 0.04), headache 10% 95% CI: 0.10 (0.08, 0.12) and myalgia was 18% 95% CI: 0.18 (0.14, 0.23), chest pain was 4% (95% CI: 0.04 (0.01, 0.06), Sore throat was 12% (95% CI: 0.12 (0.08, 0.15). Conclusion: The results of this study can serve as important criteria to be considered for screening as well as identifying suspected cases of COVID-19. These can also be helpful in formulating the guidelines for the periodic physical evaluation and for clinical management of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the possible association between survivin c.-31G>C (rs9904341) gene polymorphism and urinary system cancers by a meta-analysis approach. Methods: Standard electronic literature databases were searched to find eligible studies. The odds ratios (ORs) with 95% CIs were estimated to find the associations possibility. Results: Overall meta-analysis revealed significant associations between c.-31G>C transversion and risk of urinary tract cancers in dominant (OR: 1.34; 95% CI: 1.02–1.75; p = 0.035), recessive (OR: 1.52; 95% CI: 1.33–1.74; p < 0.001) and homozygote codominant (OR: 1.90; 95% Cl: 1.37–2.62; p < 0.001) genetic models. Conclusion: The c.-31G>C transversion might be a risk factor for urinary system cancers. However, more articles with different ethnicities will help to obtain a more accurate conclusion. [ABSTRACT FROM AUTHOR]

Objective(s): Stroke is the most common neurological disorder and genetic susceptibility has an important role in its etiology. Polymorphism in several genes such as lipoprotein lipase (LPL) is propounded as a risk for stroke. This meta-analysis investigated the association of rs285 and rs320 LPL polymorphism with stroke risk. Materials and Methods: We searched PubMed, Clarivate Analytics Web of Science, Google Scholar, and Science Direct databases for appropriate studies. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of this association. Also, the effects of four common polymorphisms (rs268, rs285, rs320, and rs328) on the molecular aspects of LPL were evaluated by in silico tools. Five studies were included in meta-analysis after screening. Results: Our data indicated that rs320 significantly decreased the risk of stroke (G vs. T: OR= 0.64, 95%CI=0.54-0.76; GG vs. TT: OR=0.47, 95%CI=0.29-0.75; TG vs. TT: OR=0.65, 95%CI=0.53-0.80; TG+GG vs. TT: OR=0.62, 95%CI=0.51-0.75; GG vs. TT+TG: OR=0.51, 95%CI=0.32-0.82). Moreover, a significant association between rs285 and diminution of stroke risk was seen (P- vs. P+: OR=0.72, 95%CI=0.58-0.91; P-P- vs. P+P+: OR=0.50, 95%CI=0.31-0.82; P+P-+P-P- vs. P+P+: OR=0.72, 95%CI=0.53-0.96; P-P- vs. P+P++P+P-: OR=0.581, 95%CI=0.369-0.916). Also, the same results were observed after stratifying, without any publication bias (PEgger>0.05). Furthermore, computational analysis revealed that rs268 and rs328 may affect the protein structure (prediction: non-neutral; score=19; expected accuracy=59%) while rs320 could affect the RNA structure (distance=0.2264, P-value=0.0534; P<0.2 is significant). Conclusion: This meta-analysis indicated that risk of stroke was decreased in rs320 and rs285 polymorphisms in the LPL gene. [ABSTRACT FROM AUTHOR]

In this paper, we evaluate the association of the human methylenetetrahydrofolate reductase (MTHFR)-G1793A transition with male infertility using a case-control study, a meta-analysis and an in silico analysis. In the case-control study, 308 blood samples (169 infertile and 139 fertile men) were collected. MTHFR-G1793A genotyping was performed by PCR-RFLP. The study revealed a significant protective association between the GA genotype (OR: 0.3737, 95%CI: 0.1874-0.7452, p = 0.0052) and A allele (OR: 0.4266, 95%CI: 0.2267-0.8030, p = 0.0083) with male infertility. Meta-analysis showed that the G1793A transition might be a protective mutation against male infertility in both A vs. G (OR: 0.608, 95%CI: 0.466-0.792, p < 0.001), and GA vs. GG (OR: 0.534, 95%CI: 0.394-0.724, p < 0.001) genetic models. In silico-analysis revealed that although G1793A could not make fundamental changes in the function and structure of MTHFR, it could modify the structure of the mRNA (Distance =0.1809, p = 0.1095; p < 0.2 is significant). The results suggest that G1793A substitution might be a protective genetic factor against male infertility. However, further case-control studies are required to provide a more robust conclusion. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a leading cause of maternal death worldwide and involves vascular endothelial dysfunction. The aim of this study was to investigate the association of the G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene and the risk of preeclampsia in a case-control design in an Iranian population, which was followed by a meta-analysis and an in silico approach. In the case-control study, 300 people including 135 pregnant women with preeclampsia and 165 healthy pregnant women were included. The genotype of G894T polymorphism was determined by the PCR-RFLP method. We searched authoritative scientific databases to find eligible studies for meta-analysis. The odds ratio with a 95% confidence interval was estimated to find the strength of the association of the mentioned polymorphism with the risk of preeclampsia. In addition, the effect of G894T transversion on eNOS gene function was evaluated by some bioinformatics tools. Our case-control data showed that the G894T polymorphism is associated with an increased risk of preeclampsia. In the meta-analysis, 33 eligible studies were included, and the results showed that the G894T polymorphism is associated with an increased risk of preeclampsia in the overall analysis and some stratified analyses. In addition, the structural analysis showed that the G894T variant can affect the splicing process as well as the protein stability. Based on the results, the aforementioned polymorphism may be a risk factor for preeclampsia and could be considered a potential molecular biomarker for screening susceptible individuals. [ABSTRACT FROM AUTHOR]

Methionine synthase (MTR) has a crucial role in DNA synthesis and methylation reactions. The aim of this study was to investigate the association of the MTR -A2756G polymorphism with idiopathic male infertility. Blood samples were collected from 217 idiopathic infertile- and 233 healthy-men, and MTR -A2756G genotyping was performed by PCR-RFLP. Meta-analysis was conducted by pooling our data with the data obtained from 6 previous studies. Also, the effects of this substitution on protein structure were evaluated by bioinformatics tools. Our study revealed the association of AG-genotype, GG-genotype, and G-allele with male infertility. Meta-analysis showed a significant association between A2756G transition and male infertility. In addition, structural analysis of the transition effect on protein revealed a significant influence on MTR function (with score: 38; expected accuracy: 66%). These findings suggest that the A2756G substitution might be a genetic risk factor and a potential biomarker for idiopathic male infertility. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) functions as a main regulatory enzyme in folate metabolism. The association of MTHFR gene Ala222Val polymorphism with male infertility in an Iranian population was investigated by undertaking a meta-analysis and in-silico approach. A genetic association study included 497 men; 242 had unexplained infertility and 255 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism was used for genotyping MTHFR -Ala222Val. OpenMeta[Analyst] software was used to conduct the analysis; 22 studies were identified by searching PubMed and the currently reported genetic association study. A novel in-silico approach was used to analyse the effects of Ala222Val substitution on the structure of mRNA and protein. Genetic association study revealed a significant association of MTHFR-222Val/Val genotype with oligozoospermia (OR 2.32; 95% CI, 1.12 to 4.78; P = 0.0451) and azoospermia (OR 2.59; 95% CI 1.09 to 6.17; P = 0.0314). Meta-analysis for allelic, dominant and codominant models showed a significant association between Ala222Val polymorphism and the risk of male infertility ( P < 0.001). In silico-analysis showed MTHFR -Ala222Val affects enzyme structure and could also change the mRNA properties ( P = 0.1641; P < 0.2 is significant). The meta-analysis suggested significant association of MTHFR -Ala222Val with risk of male infertility, especially in Asian populations. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to evaluate the association of interleukin‐17 (IL‐17) A‐197G gene polymorphism with chronic periodontitis (CP) in a case‐control study, a meta‐analysis, and an in silico approach. Methods: In the case‐control study, 122 cases with CP and 126 healthy controls were recruited; IL‐17 A‐197G genotyping was performed by polymerase chain reaction‐restriction fragment length polymorphism. In the meta‐analysis, comprehensive literature retrieval was performed on valid databases to identify relevant studies. Bioinformatics tools were employed to investigate the effects of A‐197G transition on the promoter region of IL‐17. Results: Our case‐control study revealed a significant association between IL‐17 A‐197G transition and CP. The overall meta‐analysis revealed significant associations between the IL‐17 A‐197G polymorphism and CP risk in homozygote co‐dominant and recessive models. The stratified analysis also showed a statistically significant association between the mentioned transition and CP risk in the Caucasian population. The in silico analysis revealed that the A‐197G polymorphism could make changes in protein‐binding sites of the IL‐17 promoter region. Conclusions: Our study supports that IL‐17 A‐197G transition could be a genetic risk factor for CP. However, further studies with a larger sample size among different ethnicities are required to obtain a more accurate conclusion. [ABSTRACT FROM AUTHOR]

Background: The Arg399Gln polymorphism in the X‐ray repair cross‐complementing group 1 gene (XRCC1) may alter the risk of prostate cancer (PCa). The present study aimed to investigate the association of the XRCC1‐Arg399Gln polymorphism with PCa risk in an Iranian population, as followed by a meta‐analysis and an in silico analysis. Methods: In a case–control study, 360 subjects were included (180 men with PCa and 180 healthy controls). XRCC1‐Arg399Gln genotyping was performed using the polymerase chain reaction‐restriction fragment length polymorphism method. In the meta‐analysis, 14 eligible studies were included to which our case–control data were added to estimate the pooled odds ratios. Some bioinformatics tools were employed to evaluate the effects of Arg399Gln substitution on molecular aspects of the XRCC1 protein. Results: Our case–control study revealed a significant association between the XRCC1‐Arg399Gln polymorphism and PCa risk. The data from overall meta‐analysis showed significant associations between the mentioned polymorphism and PCa risk in allelic and recessive genetic models. In addition, we observed statistically significant associations in stratified analyses by ethnicity, sample size and source of controls. Our in silico analysis showed that Arg399Gln substitution could be damaging with respect to the function and structure of the XRCC1 protein. Conclusions: Based on these results, the XRCC1‐Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men. [ABSTRACT FROM AUTHOR]

ABSTRACT Research Question Is there any genetic association between oestrogen receptor alpha [ ERα ] -PvuII polymorphism and idiopathic male infertility? Design A total of 226 infertile and 213 fertile men participated in the present case-control study. ERα-PvuII genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Meta-analysis was also performed by pooling data collected from seven other eligible studies identified by searches of PubMed, Embase, Google Scholar, and Science Direct databases. Summary odds ratios were estimated by fixed- or random-effects models. The molecular effects of ERα-PvuII polymorphism were evaluated by bioinformatics tools. Results A significant protective association was reported between ERα-PvuII and male infertility in the homozygote model [OR=0.54, 95%CI=0.3–0.98, p =0.042]. Also, a similar association was observed in asthenozoospermia subgroup [OR=0.4, 95%CI=0.18–0.9, p =0.025]. Meta-analysis also revealed that the ER-PvuII polymorphism was significantly associated with the decreased risk of male infertility in the heterozygote co-dominant model [OR=0.80, 95%CI=0.64–0.99, p =0.042]. Moreover, similar protective results were reported in stratified analyses in Caucasian subgroup in the dominant genetic model [OR=0.66, 95%CI=0.45–0.96, p =0.029] and in the heterozygote co-dominant model [OR=0.62, 95%CI=0.41–0.93, p =0.021]. A significant association was also found in studies with sample size of less than 400 subjects in heterozygote co-dominant model [OR=0.69, 95%CI=0.50–0.95, p =0.023]. The bioinformatics data indicated that ER-PvuII polymorphism could significantly affect RNA structure of ERα [ p =0.004]. Conclusion The ERα-PvuII polymorphism could be considered as a possible protective factor against male infertility. [ABSTRACT FROM AUTHOR]