Corrigendum: Dose-dependent stimulation of human follicular steroidogenesis by a novel rhCG during ovarian stimulation with fixed rFSH dosing.

[This corrects the article DOI: 10.3389/fendo.2022.1004596.].

Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.

Background: Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population. Materials and methods: We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups. Results: The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively). Conclusion: FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.

[Research progress in genetics of noise-induced hearing loss].

Noise-induced hearing loss（NIHL） is an acquired sensorineural hearing loss induced by long-term noise exposure. The susceptibility of exposed people may vary even in the same noise environment. With the development of sequencing techniques, genes related to oxidative stress, immunoinflammatory, ion homeostasis, energy metabolism, DNA damage repair and other mechanisms in NIHL have been reported continuously. And some genes may interact with noise exposure indexes. In this article, population studies on NIHL-related gene polymorphisms and gene-environment interactions in the past 20 years are reviewed, aimed to providing evidence for the construction of NIHL-related risk prediction models and the formulation of individualized interventions.

Boom-bust population dynamics drive rapid genetic change.

Increasing environmental threats and more extreme environmental perturbations place species at risk of population declines, with associated loss of genetic diversity and evolutionary potential. While theory shows that rapid population declines can cause loss of genetic diversity, populations in some environments, like Australia's arid zone, are repeatedly subject to major population fluctuations yet persist and appear able to maintain genetic diversity. Here, we use repeated population sampling over 13 y and genotype-by-sequencing of 1903 individuals to investigate the genetic consequences of repeated population fluctuations in two small mammals in the Australian arid zone. The sandy inland mouse (Pseudomys hermannsburgensis) experiences marked boom-bust population dynamics in response to the highly variable desert environment. We show that heterozygosity levels declined, and population differentiation (FST) increased, during bust periods when populations became small and isolated, but that heterozygosity was rapidly restored during episodic population booms. In contrast, the lesser hairy-footed dunnart (Sminthopsis youngsoni), a desert marsupial that maintains relatively stable population sizes, showed no linear declines in heterozygosity. These results reveal two contrasting ways in which genetic diversity is maintained in highly variable environments. In one species, diversity is conserved through the maintenance of stable population sizes across time. In the other species, diversity is conserved through rapid genetic mixing during population booms that restores heterozygosity lost during population busts.

Treatment outcome and germline predictive factors of ropeginterferon alpha-2b in myeloproliferative neoplasm patients.

BACKGROUND: Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in myeloproliferative neoplasms (MPN). However, most work originated from western countries, and data from different ethnic populations have been lacking. METHODS: To gain insights, targeted sequencing was performed to detect myeloid-associated mutations and SNPs in eight loci across three genes (IFNL4, IFN-γ, and inosine triphosphate pyrophosphatase [ITPA]) to explore their predictive roles in our cohort of 21 ropeginterferon alpha-2b (ROPEG)-treated MPN patients, among whom real-time quantitative PCR was also performed periodically to monitor the JAK2V617F allele burden in 19 JAK2V617F-mutated cases. RESULTS: ELN response criteria were adopted to designate patients as good responders if they achieved complete hematological responses (CHR) within 1 year (CHR1) or attained major molecular responses (MMR), which occurred in 70% and 45% of the patients, respectively. IFNL4 and IFN-γ gene SNPs were infrequent in our population and were thus excluded from further analysis. Two ITPA SNPs rs6051702 A>C and rs1127354 C>A were associated with an inferior CHR1 rate and MMR rate, respectively. The former seemed to be linked to grade 2 or worse hepatotoxicity as well, although the comparison was of borderline significance only (50%, vs. 6.7% in those with common haplotype, p = 0.053). Twelve patients harbored 19 additional somatic mutations in 12 genes, but the trajectory of these mutations varied considerably and was not predictive of any response. CONCLUSIONS: Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.

Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study.

SCOPE: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. METHODS AND RESULTS: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure. CONCLUSION: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.

Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience.

Background: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. Methods: We included 112 kidney recipients genotyped for CYP3A5*3, CYP3A4*1.001, and CYP3A4*22. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Results: Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A4*1/*1 (86.6%) and CYP3A5*3/*3 (77.7%) genotypes. CYP3A4*1.001 and CYP3A5*1 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A4*22 allele showed no such effect (p = 0.016, p < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. Conclusions: The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients.

Variations in the Cadherin 23 Gene Associated With Noise-Induced Hearing Loss.

Background: The relationship between CDH23 gene variants and NIHL is unclear. This study investigates the association between cadherin 23 (CDH23) gene variants and noise-induced hearing loss (NIHL). Methods: This is a case-control study. Workers who were exposed to noise from a steel factory in North China were recruited and divided into two groups: the case group (both ears' high-frequency threshold average [BHFTA] ≥40dB) and the control group (BHFTA ≤25 dB). This study used the generalised multifactor dimensionality reduction method to analyse the association among 18 single-nucleotide polymorphisms (SNPs) in CDH23 and NIHL. Logistic regression was performed to investigate the main effects of SNPs and the interactions between cumulative noise exposure (CNE) and SNPs. Furthermore, CNE was adjusted for age, gender, smoking, drinking, physical exercise and hypertension. Results: This study recruited 1,117 participants. The results showed that for rs11592462, participants who carried the GG genotype showed an association with NIHL greater than that of those who carried the CC genotype. Accordingly, genetic variation in the CDH23 gene could play an essential role in determining individual susceptibility to NIHL. Conclusion: Genetic variations in the CDH23 gene may play an important role in determining individual susceptibility to NIHL. These results provide new insight into the pathogenesis and early prevention of NIHL.

Advancing human genotyping: The Infinium HTS iSelect Custom microarray panel (Rita) development study.

Single Nucleotide Polymorphisms (SNPs), as the most prevalent type of variation in the human genome, play a pivotal role in influencing human traits. They are extensively utilized in diverse fields such as population genetics, forensic science, and genetic medicine. This study focuses on the 'Rita' BeadChip, a custom SNP microarray panel developed using Illumina Infinium HTS technology. Designed for high-throughput genotyping, the panel facilitates the analysis of over 4000 markers efficiently and cost-effectively. After careful clustering performed on a set of 1000 samples, an evaluation of the Rita panel was undertaken, assessing its sensitivity, repeatability, reproducibility, precision, accuracy, and resistance to contamination. The panel's performance was evaluated in various scenarios, including sex estimation and parental relationship assessment, using GenomeStudio data analysis software. Findings show that over 95 % of the custom BeadChip assay markers were successful, with better performance of transitions over other mutations, and a considerably lower success rate for Y chromosome loci. An exceptional call rate exceeding 99 % was demonstrated for control samples, even with DNA input as low as 0.781 ng. Call rates above 80 % were still obtained with DNA quantities under 0.1 ng, indicating high sensitivity and suitability for forensic applications where DNA quantity is often limited. Repeatability, reproducibility, and precision studies revealed consistency of the panel's performance across different batches and operators, with no significant deviations in call rates or genotyping results. Accuracy assessments, involving comparison with multiple available genetic databases, including the 1000 Genome Project and HapMap, denoted over 99 % concordance, establishing the Rita panel's reliability in genotyping. The contamination study revealed insights into background noise and allowed the definition of thresholds for sample quality evaluation. Multiple metrics for differentiating between negative controls and true samples were highlighted, increasing the reliability of the obtained results. The sex estimation tool in GenomeStudio proved highly effective, correctly assigning sex in all samples with autosomal loci call rates above 97 %. The parental relationship assessment of family trios highlighted the utility of GenomeStudio in identifying genotyping errors or potential Mendelian inconsistencies, promoting the application of arrays such as Rita in kinship testing. Overall, this evaluation confirms the Rita microarray as a robust, high-throughput genotyping tool, underscoring its potential in genetic research and forensic applications. With its custom content and adaptable design, it not only meets current genotyping demands but also opens avenues for further research and application expansion in the field of genetic analysis.

The causal effect of exposure to air pollution on risk of adverse pregnancy outcomes: A two-sample Mendelian randomisation study.

BACKGROUND: Epidemiological studies have examined the relation between air pollution (NOx, NO2, PM2.5, PM2.5-10, and PM10) and adverse pregnancy outcomes (APOs). There's increasing evidence that air pollution increases the risk of APOs. However, the results of these studies are controversial, and the causal relation remains uncertain. We aimed to assess whether a genetic causal link exists between air pollution and APOs and the potential effects of this relation. METHODS: A novel two-sample Mendelian randomisation (MR) study used pooled data from a large-scale complete genome correlation study. The primary analysis method was inverse variance weighting (IVW), which explored the expose-outcome relationship for assessing single nucleotide polymorphisms (SNPs) associated with air pollution. Further sensitivity analysis, including MR-PRESSO, MR-Egger regression, and leave-one analysis, was used to test the consistency of the results. RESULTS: There was a significant correlation between air pollution-related SNPs and APOs. A robust causal link was found between genetic susceptibility to air pollution and APOs. CONCLUSIONS: Our MR analysis reveals a genetic causal relation between air pollution and APOs, which may help provide new insights into further mechanisms and clinical studies in air pollution-mediated APOs.

Influence of genetic polymorphisms on imatinib concentration and therapeutic response in patients with chronic-phase chronic myeloid leukemia.

BACKGROUND: Diminished bioavailability of imatinib in leukemic cells contributes to poor clinical response. We examined the impact of genetic polymorphisms of imatinib on the pharmacokinetics and clinical response in 190 patients with chronic myeloid leukaemia (CML). METHODS: Single nucleotide polymorphisms were genotyped using pyrophosphate sequencing. Plasma trough levels of imatinib were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Patients carrying the TT genotype for ABCB1 (rs1045642, rs2032582, and rs1128503), GG genotype for CYP3A5-rs776746 and AA genotype for ABCG2-rs2231142 polymorphisms showed higher concentration of imatinib. Patients with T allele for ABCB1 (rs1045642, rs2032582, and rs1128503), A allele for ABCG2-rs2231142, and G allele for CYP3A5-rs776746 polymorphisms showed better cytogenetic response and molecular response. In multivariate analysis, carriers of the CYP3A5-rs776746 G allele exhibited higher rates of complete cytogenetic response (CCyR) and major molecular response (MMR). Similarly, patients with the T allele of ABCB1-rs1045642 and rs1128503 demonstrated significantly increased CCyR rates. Patients with the A allele of ABCG2-rs2231142 were associated with higher MMR rates. The AA genotype for CYP3A5-rs776746, and the CC genotype for ABCB1-rs104562, and rs1128503 polymorphisms were associated with a higher risk of imatinib failure. Patients with the G allele for CYP3A5-rs776746 exhibited a higher incidence of anemia, and T allele for ABCB1-rs2032582 demonstrated an increased incidence of diarrhea. CONCLUSIONS: Genotyping of ABCB1, ABCG2, and CYP3A5 genes may be considered in the management of patients with CML to tailor therapy and optimize clinical outcomes.

Genetic variations in exon 10 of ENAM and their association with early childhood caries.

OBJECTIVE: Enamelin is the largest enamel matrix protein encoded by the ENAM gene. The primary purpose of this study was to identify genetic variants in ENAM exon 10 that can alter susceptibility to early childhood caries (ECC). METHODS: This case-control study included 248 children aged 3-6 years, with 124 children diagnosed with ECC in the case group and 124 children without caries in the control group. Questionnaires were used to record demographic data, socioeconomic status, hygienic practices, and feeding practices, and a 24-hour diet diary was kept. Seven polymorphisms (rs7671281, rs1738668322, rs3796703, rs3796704, rs759376039, rs775159311, and rs1738678483) in ENAM exon 10 were sequenced. RESULTS: The heterozygous CT genotype of rs7671281 was significantly more common in the case group compared to the control group (odds ratio [OR], 6.1765; 95% confidence interval [CI], 2.05-18.58; P=0.0006). Under the dominant model, the TT genotype of rs7671281 was significantly more common in the control group (OR, 6.47; 95% CI, 2.15-19.39; P<0.001). The AG genotype of rs3796704 was significantly more common in the case group than in the control group (OR, 5.705; 95% CI, 1.60-20.25; P=0.006). Under the dominant model, the GG genotype of rs3796704 was significantly more common in children without caries than in children with caries (OR, 6.84; 95% CI, 1.96-23.90; P<0.001). CONCLUSIONS: The C allele of rs7671281 and the A allele of rs3796704 can increase susceptibility to ECC.

Critical Amino Acid Residues Regulating TRPA1 Zn2+ Response: A Comparative Study Across Species.

Cellular zinc ions (Zn2+) are crucial for signal transduction in various cell types. The transient receptor potential (TRP) ankyrin 1 (TRPA1) channel, known for its sensitivity to intracellular Zn2+ ([Zn2+]i), has been a subject of limited understanding regarding its molecular mechanism. Here, we employed metal ion-affinity prediction, three-dimensional structural modeling, and mutagenesis, utilizing data from the Protein Data Bank and AlphaFold Database, to elucidate the [Zn2+]i binding domain (IZD) structure composed by specific amino acid residues (AAs) in human (hTRPA1) and chicken TRPA1 (gTRPA1). External Zn2+ induced activation in hTRPA1, while not in gTRPA1. Moreover, external Zn2+ elevated [Zn2+]i specifically in hTRPA1. Notably, both hTRPA1 and gTRPA1 exhibited inherent sensitivity to [Zn2+]i, as evidenced by their activation upon internal Zn2+ application. The critical AAs within IZDs, specifically histidine at 983/984, lysine at 711/717, tyrosine at 714/720, and glutamate at 987/988 in IZD1, and H983/H984, tryptophan at 710/716, E854/E855, and glutamine at 979/980 in IZD2, were identified in hTRPA1/gTRPA1. Furthermore, mutations, such as the substitution of arginine at 919 (R919) to H919, abrogated the response to external Zn2+ in hTRPA1. Among single-nucleotide polymorphisms (SNP) at Y714 and a triple SNP at R919 in hTRPA1, we revealed that the Zn2+ responses were attenuated in mutants carrying the Y714 and R919 substitution to asparagine and proline, respectively. Overall, this study unveils the intrinsic sensitivity of hTRPA1 and gTRPA1 to [Zn2+]i mediated through IZDs. Furthermore, our findings suggest that specific SNP mutations can alter the responsiveness of hTRPA1 to extracellular and intracellular Zn2+.

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations.

N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays a crucial role in regulating mRNA expression, stability, and translation in mammals. M6A regulators have gained attention for their potential implications in tumorigenesis and clinical applications, such as cancer diagnosis and therapeutics. The existing literature predominantly addresses m6A regulators in the context of primary prostate cancer (PCa). However, a notable gap in the knowledge emerges regarding the dynamic expression patterns of these regulators as PCa progresses towards the castration-resistant stage (CRPC). Employing sequential window acquisition of all theoretical mass spectra (SWATH-MS) and RNAseq analysis, we comprehensively profiled the expression of 27 m6A regulators in hormone/androgen-dependent and -independent PCa cell lines, revealing distinct clustering between tumor and adjacent normal prostate tissues. High-grade PCa tumors demonstrated the upregulation of METTL3, RBM15B, and HNRNAPA2B1 and the downregulation of ZC3H13, NUDT21, and FTO. Notably, we identified six m6A regulators associated with PCa survival. Additionally, association analysis of the PCa-associated risk loci in the cancer genome atlas program (TCGA) data unveiled genetic variations near the WTAP, HNRNPA2B1, and FTO genes as significant expression quantitative trait loci. In summary, our study unraveled abnormalities in m6A regulator expression in PCa progression, elucidating their association with PCa risk loci. Considering the heterogeneity within the PCa phenotypes and treatment responses, our findings suggest that prognostic stratification based on m6A regulator expression could enhance PCa diagnosis and prognosis.

Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi-directional Mendelian randomization analysis.

PROBLEM: Preeclampsia, a multifaceted condition during pregnancy characterized by hypertension and organ dysfunction, poses significant risks to both maternal and fetal health. This study aims to investigate the bidirectional causal relationship between peripheral immune cell phenotypes and preeclampsia using a two-sample Mendelian randomization (MR) approach. METHOD OF STUDY: Genetic data from two sizable cohorts were utilized: 3757 individuals from Sardinia, providing information on 731 immune traits, and 200 929 Finnish adult females, encompassing 6663 preeclampsia cases. Single-nucleotide polymorphisms served as instrumental variables. The MR analyses employed the inverse variance-weighted (IVW) method as the primary tool, supplemented by MR-Egger, weighted median, and weighted mode methods to enhance reliability and address potential heterogeneity and horizontal pleiotropy. RESULTS: Among the 731 immune cell phenotypes studied, 18 displayed a suggestive positive association (IVW p < .05) with heightened preeclampsia risk, while 20 exhibited a suggestive negative association linked to reduced risk. Following false discovery rate (FDR) adjustment, four immune phenotypes showed significant associations with decreased preeclampsia risk: CD27 on CD24+ CD27+ B cells (B-cell panel) (odds ratio [OR] = 0.927, PFDR = 0.061), CD33+ HLA DR+ CD14- absolute count (OR = 0.963, PFDR = 0.061), CD80 on plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061); and CD80 on CD62L+ plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061). In the reverse-direction MR analysis, no significant causal effects of preeclampsia on immune cell phenotypes were observed. CONCLUSIONS: This study provides quantifiable evidence linking specific immune cell phenotypes to the risk of developing preeclampsia. This novel understanding of the immunological aspects underlying preeclampsia's pathogenesis could lead to innovative therapeutic strategies centered on immune modulation.

Individual genomic loci, transcript level, and biochemical profile of immune and antioxidant markers associated with genetically identified bacterial mastitis in Shami goats in Egypt.

Background: Mastitis in goats is unquestionably a grave concern, with far-reaching implications for both animal well-being and productivity, while also presenting a potential threat to public health. Aim: The study aimed to compare culture methods and multiplex PCR (m-PCR) in the detection of the most three common mastitis-causing pathogens (Staphylococcus aureus, Escherichia coli, and Streptococcus spp.) and investigate the gene expression, single nucleotide polymorphisms (SNPs), serum concentrations of immunological and antioxidant indicators linked to mastitis in Shami goats. Methods: One hundred Shami do (50 Shami goats with clinical mastitis and 50 normal goats taken as control group). The culture methods and m-PCR analysis were used to find the bacteria in the milk samples. Blood samples were obtained to assess some hemato-biochemical parameters, detect SNPs, and determine the expression of certain immunological and antioxidant indicators in the genes. Results: The culture method detected the pathogens causing mastitis in 90% of the milk samples, but m-PCR detected them in 100% of the milk samples. SNPs linked to mastitis resistance/susceptibility in examined does were detected through DNA sequencing of immunological and antioxidant indicators. The magnitude of gene expression varied significantly between the resistant and mastitis-affected groups. Significant (P ˂ 0.05) elevations were noticed in WBCs count, mainly neutsrophils count, serum levels of BHB, NEFA, triglycerides, LDL-C, AST, ALT, ALP, creatinine, total protein, globulin, Ca, K, GPx, MDA, acute phase proteins, and cytokines in mastitis affected does as compared to control. While RBCs count, PCV%, lymphocytes count, serum concentration of glucose, cholesterol, HDL-C, albumin, Na, Cl, P, GSH, SOD, and catalase significantly (P ˂ 0.05) diminished in mastitis affected does compared to healthy ones. APPs and pro-inflammatory cytokines scored high sensitivities and NPVs but TNF-α and serum amyloid A (SAA) had the highest percentages of increase. Conclusion: The study confirmed that m-PCR is the most sensitive method for bacteria identification (S. aureus, E. coli, and Strept. spp.) while SNPs in antioxidant and immunological genes may be important genetic indicators for mastitis risk or resistance in Shami does. To establish an effective management plan and forecast the most sensitive risk time for illness onset, gene expression profiles of the tested genes may also be employed as proxy biomarkers. TNF-α and SAA may be precious indicators for the detection of caprine mastitis.

The Role of FOXP3 Polymorphisms in Graves' Disease with or without Ophthalmopathy in a Turkish Population.

Objectives: Forkhead box P3 (FOXP3) gene polymorphisms have been evaluated in many autoimmune diseases, including Graves' disease (GD), in different populations. However, those polymorphisms have not been analyzed in GD or Graves' ophthalmopathy (GO) in the Turkish population. In this study, we aimed to evaluate the frequency of FOXP3 polymorphisms in GD with or without ophthalmopathy in a Turkish population. Materials and Methods: The study included 100 patients with GO, 74 patients with GD without ophthalmopathy, and 100 age- and sex-matched healthy controls. In all study participants, rs3761547 (-3499 A/G), rs3761548 (-3279 C/A), and rs3761549 (-2383 C/T) single nucleotide polymorphisms (SNPs) were detected using the polymerase chain reaction-restriction fragment length polymorphism method. The chi-square test was used to evaluate genotype and allele frequencies. Odds ratios and 95% confidence intervals were calculated for genotype and allele risks. Results: In the patient group (including GD with or without ophthalmopathy), the rs3761548 AC and AA genotype and rs3761549 CT genotype were significantly more frequent than in the control group (all p<0.05). No genotypic and allelic differences were observed for rs3761547 between the patient and control groups (all p>0.05). There was no statistically significant difference between the GO and GD without ophthalmopathy groups concerning the allele and genotype frequencies of all three FOXP3 SNPs (all p>0.05). Conclusion: The AC and AA genotypes of rs3761548 (-3279) and CT genotype of rs3761549 (-2383 C/T) were shown to be possible risk factors for GD development in the Turkish population. However, none of the three SNPs was shown to be associated with the development of GO in patients with GD.

Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

EGR3 Polymorphism Is a Potential Susceptibility Factor of Schizophrenia Risk in a Chinese Population.

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) (EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.