scholarly journals Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Enrique Ortega ◽  
Sujhey Hernández-Bazán ◽  
Beatriz Sánchez-Hernández ◽  
Ileana Licona-Limón ◽  
Javier Fuentes-Dominguez
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genetic Model ◽  
Public Health Problem ◽  
Active Tuberculosis ◽  
The State ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Tuberculosis Disease ◽  
Active Disease

Tuberculosis is still a global public health problem, with an estimated 10 million new cases and 1.6 million deaths in 2017. Of all humans infected with M. tuberculosis, only 10-15% will develop active tuberculosis disease during their lifetime, and data suggest that along with environmental factors, genetic factors influence susceptibility to develop active disease. Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the initiation and shaping of adaptive immune responses, and several TLRs have been shown to recognize mycobacterial components. In this work, we performed a case-control study to determine if common single nucleotide polymorphisms (SNPs) in genes encoding TLRs 1, 2, 4, 6, and 10 are associated with susceptibility to develop active tuberculosis in population from the state of Veracruz, Mexico. The study included 279 cases and 569 controls. The results show that the frequency of two SNPs in TLR4 was significantly higher in controls than in tuberculosis patients. The minor allele (G) of rs4986790 in TLR4 (D299G) decreased the risk of active tuberculosis in the allelic (A vs. G, OR=0.31, 95%CI=0.09‐0.81, p=0.01) and in the dominant genetic model (AA vs. GG+AG, OR=0.26, 95%CI=0.09‐0.77, p=0.02). Similarly, the minor allele (T) of rs4986791 in TLR4 (T399I) decreased the risk of active disease in the allelic model (C vs. T, OR=0.29, 95%CI=0.10‐0.90, p=0.03). We did not find an association of SNPs in TLR1 (N248S), TLR2 (R753Q), TLR6 (S249P), and TLR10 (A153S and V298I) with tuberculosis disease. These results suggest that in this population, genetic variants of TLR4 affect the susceptibility for suffering active tuberculosis disease.

scholarly journals Single Nucleotide Polymorphisms in IFN-γ Signaling Pathway Associated with Risk of Hepatitis B Virus Infection in Chinese Children

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Zhuo ◽  
Yalan Yang ◽  
Mingjun Zhang ◽  
Ying Xu ◽  
Zhongping Chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Single Nucleotide Polymorphisms ◽  
Signaling Pathway ◽  
Public Health Problem ◽  
Hbv Infection ◽  
Nucleotide Polymorphisms ◽  
Breakthrough Infection ◽  
Single Nucleotide ◽  
B Virus

Hepatitis B virus (HBV) infection is a challenging public health problem in China and worldwide. Mother-to-child transmission is one of the main transmission routes of HBV in highly endemic regions. However, the mechanisms of HBV perinatal transmission in children have not been clearly defined. The aim of this study was to demonstrate the association between single-nucleotide polymorphisms (SNPs) in IFN-γ signaling pathway and HBV infection or breakthrough infection in children. Two hundred and seventy-four HBV-infected children defined as test positive for hepatitis B surface antigen (HBsAg) and 353 controls defined as negative for HBsAg in China were recruited from October 2013 to May 2015. SNPs in IFN-γ signaling pathway including IFNG, IFNGR1, IFNGR2, and IL12B were genotyped. Rs2234711 in IFNGR1 was significantly associated with HBV infection in children (OR = 0.641, 95% CI: 0.450–0.913). In addition, rs2234711 was also significantly associated with HBV breakthrough infection in children born to HBsAg-positive mothers (OR = 0.452, 95% CI: 0.205–0.998). Our study confirmed that genetic variants in IFN-γ signaling pathway have significant associations with HBV infection, especially with HBV breakthrough in children. This study provides insight into HBV infection in children and could be used to help design effective strategies for reducing immunoprophylaxis failure.

scholarly journals OR24-05 Identifying Regulatory Elements Within a Novel Enhancer of FSHB Containing Two PCOS-Associated Single Nucleotide Polymorphisms

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Stephanie C Bohaczuk ◽  
Varykina G Thackray ◽  
Pamela L Mellon
Keyword(s):  
Transcription Factor ◽  
Single Nucleotide Polymorphisms ◽  
Regulatory Elements ◽  
Minor Allele ◽  
Specific Marker ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Alcoholic Fatty Liver ◽  
Conserved Region

Abstract Polycystic ovary syndrome (PCOS) is the most common cause of female infertility, affecting approximately 10 percent of women by Rotterdam criteria, and is comorbid with obesity, type II diabetes, hypertension, and non-alcoholic fatty liver disease. As twin studies reveal that genetics account for approximately 70% of PCOS risk, genome-wide association studies (GWAS) can provide powerful insight into PCOS etiology. PCOS GWAS studies from several populations identified a risk locus containing the FSHB gene, which encodes the beta subunit of follicle-stimulating hormone (FSH). As FSH supplementation can restore ovulation in some PCOS patients, deficient FSH signaling could be a causative factor of anovulation and potentially other facets of PCOS. Two of the lead single nucleotide polymorphisms (SNPs) in association with PCOS, rs11031005 and rs11031006, fall within a highly conserved genomic region in mammals. We hypothesized that the conserved region (~450 base pairs) enhances FSHB transcription, and that one or both PCOS-related SNPs alter its function. We have shown that the conserved region from both human and mouse can act as an enhancer of FSHB in LβT2 cells, an immortalized, mouse-derived, mature pituitary gonadotrope cell line, and that its function is altered by the rs11031006 minor allele through modification of an SF1 consensus site. As elimination of the SF1 site reduced but did not completely abolish the function of the enhancer, we continued our investigation to identify additional regulatory sites. Transient transfection of LβT2 cells revealed a possible role for the rs11031005 SNP in FSHB regulation, with the minor allele decreasing enhancer-mediated FSHB transcription. This effect may be due to decreased binding of an unidentified transcription factor, as gel shift revealed that the rs11031005 minor allele reduced the intensity of a binding complex. Using truncations and sliding deletions, we identified three additional putative transcription factor binding sites with consensus sequences for ZEB1, PTX1, and SMAD. To support a role for the conserved region as an enhancer in native chromatin, we assessed the histone status in LβT2 chromatin. Compared to the proximal Fshb promoter, the enhancer-specific marker, H3K4me1, was enriched near the conserved region. Neither promoter/enhancer markers of active (H3K27Ac) or repressed (H3K27me3) chromatin were enriched near the conserved region, although levels of both modifications were consistent with the Fshb proximal promoter. Overall, our data support the role of this conserved region as a novel regulator of FSHB/Fshb transcription and reveal a possible mechanism to explain the contribution of PCOS-associated SNPs through FSHB regulation.

scholarly journals Multiple Infectious Complications in a Severely Injured Patient with Single Nucleotide Polymorphisms in Important Innate Immune Response Genes

2015 ◽  
Vol 9 (1) ◽  
pp. 367-371
Author(s):  
Maarten W.G.A. Bronkhorst ◽  
Peter Patka ◽  
Esther M.M. Van Lieshout
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Public Health Problem ◽  
Injured Patient ◽  
Severe Trauma ◽  
Infectious Complications ◽  
Innate Immune ◽  
Major Public Health Problem ◽  
Trauma Patients ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Trauma is a major public health problem worldwide. Infectious complications, sepsis, and multiple organ dysfunction syndrome (MODS) remain important causes for morbidity and mortality in patients who survive the initial trauma. There is increasing evidence for the role of genetic variation in the innate immune system on infectious complications in severe trauma patients. We describe a trauma patient with multiple infectious complications caused by multiple micro-organisms leading to prolonged hospital stay with numerous treatments. This patient had multiple single nucleotide polymorphisms (SNPs) in the MBL2, MASP2, FCN2 and TLR2 genes, most likely contributing to increased susceptibility and severity of infectious disease.

scholarly journals Διαβητική αμφιβληστροειδοπάθεια σε Έλληνες καυκάσιους πάσχοντες από διαβήτη τύπου 2, συσχέτιση με τον πολυμορφισμό στο γονίδιο του αναστολέα του ενεργοποιητή του πλασμινογόνου 1 (ΡAI 1)

2017 ◽  
Author(s):  
Θωμάς Σοκολάκης
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Odds Ratio ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pai 1

Ιστορικό: Υπαρχουν συσσωρεύμενα στοιχεία για την ύπαρξη γενετικής ευαισθησίας στην ανάπτυξη διαβητικής αμφιβληστροειδοπάθειας (ΔΑ). Ο ρόλος του αναστολέα του ενεργοποιητή του πλασμινογόνου-1 (PAI-1) στον κινδυνο αναπτυξης ΔΑ παραμένει αμφιλεγόμενος.Σκοπός: Η παρούσα μελέτη σχεδιάστηκε για να διερευνήσει την πιθανή επίδραση των πολυμορφισμών της περιοχής του γονιδίου PAI-1 στον κίνδυνο ανάπτυξης της ΔΑ και στον κίνδυνο ανάπτυξης ΔΑ πρώιμα έναντι καθυστερημένα κατά τη διάρκεια του σακχαρώδους διαβήτη τύπου 2 (ΣΔ2). Μέθοδοι: Συνολικά 138 ασθενείς με ΔΑ, 107 ασθενείς με ΣΔ2 χωρίς ΔΑ και 315 υγιείς μάρτυρες προσλήφθηκαν. Για να καλυφθεί η πλειοψηφία της γενετικής μεταβλητότητας στην εκτεταμένη περιοχή του γονιδίου ΡΑΙ-1, πέντε πολυμορφισμοί μονού νουκλεοτιδίου (single-nucleotide polymorphisms SNPs) από το HapMap χρησιμοποιώντας μια προσέγγιση ανά ζεύγη και r2> 0,8 και μία μικρή συχνότητα αλληλόμορφων (minor allele frequency MAF)> 0,05 εντοπίστηκαν. Χρησιμοποιώντας αναλύσεις λογιστικής παλινδρόμησης, ετικέτες SNPs και απλότυποι δοκιμάστηκαν για ενώσεις με κίνδυνο ανάπτυξης ΔΑ και με κίνδυνο ανάπτυξης ΔΑ νωρίς ή αργά κατά τη διάρκεια του ΣΔ2. Ο γενικευμένος λόγος πιθανότητας (generalized odds ratio ORG) υπολογίστηκε για την εκτίμηση της επίδρασης μεταλλακτικού φορτίου στην ανάπτυξη ΔΑ μεταξύ όλων των συμμετεχόντων. Διενεργήθηκαν διορθώσεις για πολλαπλές συγκρίσεις (p-τιμή <0,01).Αποτελέσματα: Ένα σημαντικό αποτέλεσμα του rs2070682 στον κίνδυνο πρόωρης έναρξης ΔΑ βρέθηκε στο συνκυριαρχο μοντέλο κληρονομικότητας [αναλογία πιθανότητας, OR (95% διάστημα εμπιστοσύνης, CI): 5.04 (1.47-17.28), p = 0.018]. Ωστόσο, αυτή η σχέση οριακά δεν επιβίωσε πολλαπλών διορθώσεων και δοκιμών. Δεν αποκαλύφθηκε καμία άλλη σημαντική συσχέτιση μεταξύ των επισημάνσεων-SNPs και των απλοτύπων ΡΑΙ-1. Επιπλέον, δεν βρέθηκε σημαντική επίδραση του μεταλλακτικού φορτίου της ετικέττας SNPs στον PAI-1 στον κίνδυνο ανάπτυξης ΔΑ στη διαρκεια του ΣΔ2. Συμπεράσματα: Συμπερασματικά, η παρούσα μελέτη δεν παρέχει καμία ισχυρή απόδειξη ότι οι παραλλαγές του γονιδίου PAI-1 εμπλέκονται στον κίνδυνο ανάπτυξης της ΔΑ ή στην ανάπτυξη της ΔΑ κατά τη διάρκεια του ΣΔ2.

scholarly journals Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

2020 ◽  
Author(s):  
Xiufang Xing ◽  
Yongyu Bai ◽  
Kai Sun ◽  
Min Yan
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Pain Perception ◽  
Single Port ◽  
Thoracoscopic Surgery ◽  
Clinical Problem ◽  
Minor Allele ◽  
Chinese Patients ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk

Abstract Background: Postoperative inadequate analgesia following video-assisted thoracoscopic surgery (VATS) is a common and significant clinical problem. While genetic polymorphisms may play role in the variability of postoperative analgesia effect, few studies have evaluated the associations between genetic mutations and inadequate analgesia after single-port VATS. Methods: Twenty-eight single nucleotide polymorphisms (SNPs) among 18 selected genes involved in pain perception and modulation were genotyped in 198 Chinese patients undergoing single-port VATS. The primary outcome was the occurrence of inadequate analgesia in the first night and morning after surgery which was defined by a comprehensive postoperative evaluation. Multivariable logistic regression analyses were used to identify the association between genetic variations and postoperative inadequate analgesia. Results: The prevalence of postoperative inadequate analgesia was 45.5% in the present study. After controlling for age and education level, association with inadequate analgesia was observed in four SNPs among three genes encoding voltage-gated sodium channels. Patients with the minor allele of rs33985936 (SCN11A), rs6795970 (SCN10A), and 3312G>T (SCN9A) have an increased risk of suffering from inadequate analgesia. While the patients carrying the minor allele of rs11709492 (SCN11A) have lower risk experiencing inadequate analgesia. Conclusions: We identified that SNPs in SCN9A, SCN10A, and SCN11A play a role in the postoperative inadequate analgesia after single-port VATS. Although future larger and long-term follow up studies are warranted to confirm our findings, the results of the current study may be utilized as predictors for forecasting postoperative analgesic effect for patients receiving this type of surgery.Trial registration: This study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03916120) on April 16, 2019.

Association of single nucleotide polymorphisms (SNPs) in SULT1E1 with response to treatment with abiraterone acetate (AA) in men with metastatic castration refractory prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 222-222
Author(s):  
Tyler Howard Buckley ◽  
Anitha Alex ◽  
James M. Farnham ◽  
David Gill ◽  
Shiven B. Patel ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Gleason Score ◽  
Multiple Testing ◽  
Genetic Model ◽  
Hazard Analysis ◽  
Predictive Biomarkers ◽  
Abiraterone Acetate ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

222 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict response to AA in men with mCRPC, serve as prognostic and predictive biomarkers, and guide towards more individualized therapy. Methods: 836 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 61 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to treatment failure (TTF) in 68 Caucasian men with mCRPC undergoing treatment with AA. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Three SNPs in SULT1E1 were associated with TTF on AA therapy after correcting for multiple testing (p < .00007) while controlling for Gleason Score (Table). Conclusions: SNPs in SULT1E1(estrogen sulfotransferase gene) were significantly associated with TTF on AA therapy, and may serve as predictive markers to treatment with AA. Further validation is being performed in a larger cohort of men with mCRPC. [Table: see text]

Single Nucleotide Polymorphisms in the Arginase 1 and 2 Genes Are Differentially Associated with Circulating l-Arginine Concentration in Unsupplemented and l-Arginine–Supplemented Adults

2020 ◽  
Author(s):  
Juliane Hannemann ◽  
Leonard Rendant-Gantzberg ◽  
Julia Zummack ◽  
Jonas Hillig ◽  
Ina Eilermann ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Single Nucleotide Polymorphisms ◽  
Functional Relation ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Supplement Use ◽  
Arginase 1 ◽  
Study Results ◽  
Arginine Concentration

ABSTRACT Background Genetic variation in arginase may underlie variability in whole blood l-arginine concentrations in unsupplemented and l-arginine–supplemented adults. Objectives We aimed to study whether single nucleotide polymorphisms (SNPs) in the arginase 1 (ARG1) and arginase 2 (ARG2) genes are associated with blood l-arginine concentrations in unsupplemented and l-arginine–supplemented individuals. Methods In 374 adults (mean ± SD age: 59.6 ± 14.6 y; 180 males), we analyzed SNPs in the ARG1 (rs2246012 and rs2781667) and ARG2 genes (rs3742879 and rs2759757) and their associations with blood l-arginine concentrations. We analyzed associations of haplotypes for the ARG1 gene and for the ARG1 and ARG2 genes combined with blood l-arginine concentrations in supplement users and unsupplemented participants. Results Of study participants, 120 had low (&lt;42 μmol/L), 133 had medium (42–114 μmol/L), and 121 had high blood l-arginine concentrations (&gt;114 μmol/L); 58 individuals were current l-arginine supplement users. We found a significantly higher prevalence of the minor allele of ARG1 rs2246012 in supplement users with higher blood l-arginine concentrations (P = 0.03). Mean ± SEM l-arginine concentration was 263 ± 9.76 μmol/L in supplement users homozygous for the minor allele of ARG1 rs2246012 (P = 0.004); it was 70.4 ± 25.6 μmol/L in unsupplemented participants homozygous for the minor allele of ARG2 rs3759757 (P = 0.03). The ARG1 haplotype was significantly associated with blood l-arginine concentrations in supplement users (P = 0.046), whereas the combined ARG1/ARG2 haplotype was significantly associated with blood l-arginine concentrations in the cohort as a whole (P = 0.012). Conclusions Genetic variability in the ARG1 and ARG2 genes is associated with blood l-arginine concentrations in humans: ARG1 is associated with blood l-arginine concentrations in l-arginine supplement users, whereas ARG2 is associated with blood l-arginine concentrations in unsupplemented participants. Our study is the first to describe a possible functional relation between ARG1 and ARG2 SNPs and blood l-arginine concentrations; genetic variability in ARG1 may explain variation in blood l-arginine concentrations during supplement use and discrepant study results.

scholarly journals FADS and PPARG2 Single Nucleotide Polymorphisms are Associated with Plasma Lipids in 9-Mo-Old Infants

2019 ◽  
Vol 149 (5) ◽  
pp. 708-715 ◽  
Author(s):  
Lotte Lauritzen ◽  
Ingvild D Amundsen ◽  
Camilla T Damsgaard ◽  
Mads V Lind ◽  
Theresia M Schnurr ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Single Nucleotide Polymorphisms ◽  
Ldl Cholesterol ◽  
Plasma Lipids ◽  
Hdl Cholesterol ◽  
Potential Effect ◽  
Effect Modification ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

ABSTRACT Background Dietary intake of polyunsaturated fatty acids (PUFAs), e.g., linoleic acid and n–3 (ω-3) long-chain PUFAs, has been shown in adults to affect plasma cholesterol and triglycerides (TGs), respectively. Little is known about the effects of PUFAs on plasma lipids in early life. Objective The aim of this study was to explore the associations between plasma concentrations of total, LDL, and HDL cholesterol and TGs in infants and 2 single nucleotide polymorphisms (SNPs) in the fatty acid desaturase genes (FADS) oppositely associated with docosahexaenoic acid (rs1535 and rs174448) and potential effect modification by a functional peroxisome proliferator-activated receptor-γ2 gene variant (PPARG2 Pro12Ala). Methods In 9-mo-old infants (n = 561) from 3 Danish cohorts, we analyzed associations between plasma lipids, erythrocyte PUFAs, and FADS SNPs, and interactions with PPARG2 Pro12Ala genotype, by multiple linear regression. We also examined potential effect modification by breastfeeding, as 46% of the infants were still being breastfed. Results Minor allele carriage of rs174448 was associated with lower total cholesterol (difference: −0.22 mmol/L; 95% CI: −0.37, −0.06 mmol/L; P = 0.006) and LDL cholesterol (difference: −0.15 mmol/L; 95% CI: −0.29, −0.01 mmol/L; P = 0.035), but no associations were observed with TGs or for rs1535. Minor allele carriage of both FADS SNPs was associated with 1 SD lower HDL cholesterol, but only in currently breastfed infants (rs174448 × breastfeeding, P = 0.080; rs1535 × breastfeeding, P = 0.030) and PPARG2 minor allele carriers (rs174448 × PPARG2, P = 0.001; rs1535 × PPARG2, P = 0.004). Erythrocyte arachidonic acid and eicosapentaenoic acid were inversely associated with LDL cholesterol [estimated effect (β): −0.3 mmol/L; 95% CI: −0.06, −0.00 mmol/L per percentage of fatty acids (FA%); P = 0.035] and TGs (β: −0.23 mmol/L; 95% CI: −0.41, −0.05 mmol/L per FA%; P = 0.015), respectively. Conclusions The observed associations with FADS variants indicate that PUFAs are involved in plasma lipid regulation in 9-mo-old infants. Observed FADS SNP differences and interactions with breastfeeding and PPARG2 warrant additional studies to explore the effects of individual FADS SNPs on PUFA status and potential genetic modification of dietary PUFA effects.

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