Pharmacogenomic determinants of cetuximab and oxaliplatin pharmacokinetics during combined intravenous cetuximab (IV-Cet) and triplet hepatic artery chronomodulated infusion in patients (pts) with initially unresectable liver metastases from colorectal cancer (uLM-CRC) (EU OPTILIV trial).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14082-e14082
Author(s):  
Abdoulaye Karaboue ◽  
Raphael Saffroy ◽  
Christophe Desterke ◽  
Mohamed Bouchahda ◽  
Pasquale Innominato ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Performance Status ◽  
Systemic Exposure ◽  
Fisher Exact Test ◽  
Hematologic Toxicity ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Polymorphic Genes ◽  
Direct Exposure ◽  
Polymorphic Gene

e14082 Background: Triplet HAI with IV-Cet achieved 29.7% complete uLM-CRC resections (R0+R1) and an overall median survival (OS) of 25.7 months in previously treated pts. While the high antitumour efficacy of this new regimen involved direct exposure of LM to the HAI drugs and their potentiation by cetuximab, haematological and intestinal toxicities mostly related to systemic exposure (Lévi, Ann Oncol 2016; Clin Pharmacokin 2016). Methods: To identify potential pharmacogenomics (PG) determinants of toxicity-related systemic exposure to the HAI drugs, 207 single nucleotide polymorphisms (SNPs) from 34 pharmacology genes were analysed in blood mononuclear cells (ADME PGx, MassArray platform, Sequenom, USA) from 11 pts undergoing a first course of chronomodulated triplet HAI and iv-CET (Levi et al. Clin Pharmacokinet 2016). Relations between SNPs and main pharmacokinetics parameters and toxicities were determined using ANOVA or Fisher Exact test. Results: Nine toxicity-related polymorphic genes were identified in the 52 pts of the PG study (ASCO, submitted). Here we investigated whether any of these polymorphic genes modified PK in 4F and 7M (33-72 yo) with WHO performance status 0-1. ABCB1 (rs1045642) was the only polymorphic gene that was significantly associated with both pharmacokinetics and toxicity in this study population. Conclusions: ABCB1 polymorphisms might contribute to the systemic hematologic toxicity of the combined IV-HAI regimen through altering cetuximab and oxaliplatin disposition, yet without affecting efficacy. Consideration of ABCB1 polymorphism could help optimize OPTILIV delivery in individual patients. Clinical trial information: NCT00852228. [Table: see text]

Vitamin K epoxide reductase complex subunit 1 (VKORC1): A pharmacogenomic predictor of response and survival in patients (pts) on triplet hepatic artery infusion (HAI) and intravenous cetuximab (IV-Cet) for initially unresectable liver metastases from colorectal cancer (uLM-CRC) (EU trial OPTILIV).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2569-2569
Author(s):  
Francis Levi ◽  
Raphael Saffroy ◽  
Abdoulaye Karaboue ◽  
Christophe Desterke ◽  
Valerie Boige ◽  
...  
Keyword(s):  
Vitamin K ◽  
Mononuclear Cells ◽  
Performance Status ◽  
Early Response ◽  
Hepatic Artery Infusion ◽  
Nucleotide Polymorphisms ◽  
R1 Resection ◽  
Nat2 Polymorphism ◽  
Warfarin Dosing ◽  
C 30

2569 Background: The HAI of Irinotecan-Oxaliplatin-5-Fluorouracil (IFO) with IV-Cet achieved 29.7% complete uLM-CRC resections (R0+R1) and an overall median survival (OS) of 25.7 months in previously treated pts (Lévi, Ann Oncol 2016). Methods: To identify pharmacogenomic predictors of outcomes, 207 single nucleotide polymorphisms (SNPs) from 34 pharmacology genes were analysed in blood mononuclear cells (ADME PGx, MassArray platform, Sequenom, USA). Relations between SNPs and tumor response, R0+R1, survival, and toxicities were tested using adjusted Mann Whitney, Fisher Exact, Log Rank tests and Hardy-Weinberg Equilibrium. Results: Pts (16F;36M; 33-76 yo; WHO performance status 0-1) received protocol treatment as 2nd (21 pts) or 3-4thline (31 pts). VKORC1 SNPs in promoter (rs9923231) and intron (rs9934438) were consistently associated with early and objective responses, and overall survival. For rs9923231, T/T (N = 8) as compared to C/T (N = 21) had greatest chance of achieving early response (50% vs 5%, p = 0.029) or 4-y survival (46% vs 0%, p = 0.006). VKORC1 SNPs also related to HA thrombosis (rs992331, T/T, 77% vs C/C, 30%, p = 0.04). In contrast, NAT2 SNPs (rs1041983 and rs1801280) were associated with up to 5-fold differences in R0-R1 resection rate. Statistically significant associations (p < 0.05) of SNPs with clinical outcomes were found for oxydo-reduction (CYP2E1 and HA thrombosis; CYP2C9 and diarrhea; CYP2C19 and diarrhea, fatigue, and early response), conjugation (UGT1A1 and diarrhea; NAT2 and fatigue); and transport (ABCB1 or SLC0B3 and neutropenia; SLC22A1 and diarrhea; SLC 15A2 and early response). Conclusions: VKORC1 was highlighted for the first time, as a pharmacogenomic predictor of HAI efficacy for LM-CRC. Conversion-to-resection was associated with NAT2 polymorphism. VKORC1 γ-carboxylates vitamin K-dependent proteins. Its polymorphism guides personalized warfarin dosing. VKORC1 SNPs determination could help identify the uLM-CRC pts who best benefit from intensive HAI therapy. Clinical trial information: NCT00852228.

scholarly journals 3DBIONOTES v3.0: crossing molecular and structural biology data with genomic variations

2019 ◽  
Vol 35 (18) ◽  
pp. 3512-3513 ◽  
Author(s):  
Joan Segura ◽  
Ruben Sanchez-Garcia ◽  
C O S Sorzano ◽  
J M Carazo
Keyword(s):  
Gene Annotation ◽  
Supplementary Information ◽  
Fisher Exact Test ◽  
Nucleotide Polymorphisms ◽  
Contingency Analysis ◽  
Exact Test ◽  
Genomic Variants ◽  
Protein Protein Interaction ◽  
Processing Centre ◽  
Critical Regions

Abstract Motivation Many diseases are associated to single nucleotide polymorphisms that affect critical regions of proteins as binding sites or post translational modifications. Therefore, analysing genomic variants with structural and molecular biology data is a powerful framework in order to elucidate the potential causes of such diseases. Results A new version of our web framework 3DBIONOTES is presented. This version offers new tools to analyse and visualize protein annotations and genomic variants, including a contingency analysis of variants and amino acid features by means of a Fisher exact test, the integration of a gene annotation viewer to highlight protein features on gene sequences and a protein–protein interaction viewer to display protein annotations at network level. Availability and implementation The web server is available at https://3dbionotes.cnb.csic.es Supplementary information Supplementary data are available at Bioinformatics online. Contact Spanish National Institute for Bioinformatics (INB ELIXIR-ES) and Biocomputing Unit, National Centre of Biotechnology (CSIC)/Instruct Image Processing Centre, C/ Darwin nº 3, Campus of Cantoblanco, 28049 Madrid, Spain.

Assessment of of twenty-five variants of polymorphic genes for lipid and carbohydrate metabolism, vascular inflammation and the neurotransmitter system in the first non-cardioembolic ischemic stroke

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V.N Shishkova ◽  
T.V Adasheva ◽  
L.V Stakhovskaya ◽  
A.Y.U Remennic ◽  
V.V Valyaeva
Keyword(s):  
Ischemic Stroke ◽  
Vascular Inflammation ◽  
Funding Source ◽  
Nucleotide Polymorphisms ◽  
Taqman Probes ◽  
Polymorphic Genes ◽  
Significant Difference ◽  
Polymorphic Gene ◽  
The Relationship ◽  
Bdnf Rs6265

Abstract   The study of the relationship between various of gene polymorphism: APOA-V (rs34282181), APOA-V (rs619054), APOC-IV (rs1132899), LPL (rs199675233), LP(a) (rs41267817), APOB (rs1042031), APOB (rs676210), APOC-IV (rs1132899), APOH (rs4581), ANGPT4 (rs1044250), APOE (rs5174), APOE (rs 7412), APOE (rs 429358), APOD (rs7659), ADIPOQ (rs17366743), ADIPOQ (rs185847354), ADIROR (rs12342), TNFα (rs1800620), VEGFA (rs 62401172), IL6 (rs56383910), IL8 (rs1803205), MTHFR (rs1801131), MTHFR (rs1801133), GRM 1 (rs1047005), GRM 3 (rs2228595), BDNF (rs6265) and the development of the first non-cardioembolic ischemic stroke Material and methods The alleles frequencies and genotypes assessed for 25 mono-nucleotide polymorphic gene variants in 206 patients, who had first non-cardioembolic ischemic stroke, and 206 persons with no stroke, comparable with age, gender, place of living and ethnicity. Genotyping of polymorphisms was done with the prepared TaqMan probes. Genotyping of single nucleotide polymorphisms of genes: APOA-V (rs34282181), APOA-V (rs619054), APOC-IV (rs1132899), LPL (rs199675233), LP(a) (rs41267817), APOB (rs1042031), APOB (rs676210), APOC-IV (rs1132899), APOH (rs4581), ANGPT4 (rs1044250), APOE (rs5174), APOE (rs 7412), APOE (rs 429358), APOD (rs7659), ADIPOQ (rs17366743), ADIPOQ (rs185847354), ADIROR (rs12342), TNFα (rs1800620), VEGFA (rs 62401172), IL6 (rs56383910), IL8 (rs1803205), MTHFR (rs1801131), MTHFR (rs1801133), GRM 1 (rs1047005), GRM 3 (rs2228595), BDNF (rs6265) using ready-made TaqMan probes was carried out. Results For polymorphisms ApoD (rs7659), ApoA5 (rs619054), ApoB (rs676210), IL8 (rs1803205) there was significant difference between groups in the variety of minor alleles and genotypes. Conclusions There is significant relation of mononucleotide polymorhpisms of the genes APOD (rs7659), ApoA5 (rs619054), ApoB (rs676210), IL8 (rs1803205) with the development of the first non-cardioembolic ischemic stroke In the studied groups. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Moscow Center for Neurorehabilitation

Venous Thromboembolism and High Grade Gliomas

1993 ◽  
Vol 70 (03) ◽  
pp. 393-396 ◽  
Author(s):  
Mandeep S Dhami ◽  
Robert D Bona ◽  
John A Calogero ◽  
Richard M Hellman
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Medical Center ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Fisher Exact Test ◽  
High Grade ◽  
Chi Square ◽  
Exact Test ◽  
High Grade Gliomas

SummaryA retrospective study was done to determine the incidence of and the risk factors predisposing to clinical venous thromboembolism (VTE) in patients treated for high grade gliomas. Medical records of 68 consecutive patients diagnosed and treated at Saint Francis Hospital and Medical Center from January 1986 to June 1991 were reviewed. The follow up was to time of death or at least 6 months (up to December 1991). All clinically suspected episodes of VTE were confirmed by objective tests. Sixteen episodes of VTE were detected in 13 patients for an overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher exact test) were statistically significant risk factors for the development of VTE. Thrombotic events were more likely to occur in the paretic limb and this difference was statistically significant (p = 0.00049, chi square test, with Yates correction). No major bleeding complications were seen in the nine episodes treated with long term anticoagulation.We conclude that venous thromboembolic complications are frequently encountered in patients being treated for high grade gliomas and the presence of paresis and the administration of chemotherapy increases the risk of such complications.

Electronic cigarettes: How confident and effective are allergists, pulmonologists, and primary care physicians in their practice behavior?

2020 ◽  
Vol 41 (3) ◽  
pp. 192-197
Author(s):  
Sherry S. Zhou ◽  
Alan P. Baptist
Keyword(s):  
Primary Care ◽  
Primary Care Physicians ◽  
Electronic Cigarettes ◽  
The United States ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Knowledge And Beliefs ◽  
Tobacco Cigarette ◽  
Number Of Patients ◽  
Personal Use

Background: There has been a striking increase in electronic cigarette (EC) use in the United States. The beliefs and practices toward ECs among physicians are unknown. Objective: The purpose of this study was to investigate EC practice patterns among allergists, pulmonologists, and primary care physicians. Methods: An anonymous survey was sent to physicians. The survey contained 32 questions and addressed issues related to demographics, cessation counseling behaviors, personal use, and knowledge and beliefs about ECs. Statistical analysis was performed by using analysis of variance, the Pearson χ2 test, Fisher exact test, and logistic regression. Results: A total of 291 physicians completed the survey (222 primary care physicians, 33 pulmonologists, and 36 allergists) for a response rate of 46%. The allergists asked about tobacco cigarette use as frequently as did the pulmonologists and more than the primary care physicians (p < 0.001), but they rarely asked about EC use. The pulmonologists scored highest on self-reported knowledge on ECs, although all the groups answered <40% of the questions correctly. The allergists did not feel as comfortable about providing EC cessation counseling as did the pulmonologists and primary care physicians (p < 0.001). All three groups were equally unlikely to recommend ECs as a cessation tool for tobacco cigarette users. Conclusion: Allergists lacked knowledge and confidence in providing education and cessation counseling for EC users. As the number of patients who use these products continues to increase, there is an urgent need for all physicians to be comfortable and knowledgeable with counseling about ECs.

Perbedaan Kontaminasi Bacteria Staphylococcus sp di Denominasi Uang Kertas Rupiah di Warung Jalan Adi Sucipto Kota Pontianak

2018 ◽  
Vol 1 (2) ◽  
pp. 166
Author(s):  
Sutriswanto Sutriswanto ◽  
Sugito Sugito
Keyword(s):  
Research Method ◽  
Sampling Technique ◽  
Cluster Sampling ◽  
Fisher Exact Test ◽  
Infectious Agents ◽  
Exact Test ◽  
Purposive Sampling ◽  
Paper Money

Abstract: Staphylococcus is a cause of infection. Infection can be transmitted from a source by an indirect through fomite. Paper money can act as transmission of infectious agents, money acts as a fomite. Smaller denominations of value have higher contamination. This study aims to analyze differences in contamination bacterial Staphylococcus sp on denomination of paper money Rp.2.000, 5.000, Rp.10,000 and Rp.20.000 that currently shop on Adi Sucipto street town Pontianak. The research method used in this research is in the form of difference and the sample in this research is denomination of paper money curently with sampling technique using cluster sampling. Checkup of Staphylococcus spon denomination of paper money using rinse method. On these result of study, denomination of paper money Rp.2.000 that is contaminated staphylococcus sp is 80%, denomination of paper money Rp.5.000 that is contaminated staphylococcus sp is 70%, denomination of paper money Rp.10.000 and Rp.20.000 that is contaminated staphylococcus sp is 80%. The data from result of study has been obtained were analyzed statistically by using fisher exact test, the result of p (0,477) >α (0,05) which mean as H1 is rejected. So it can be concluded there is no difference of contamination bacteria staphylococcus sp on denominations of paper money rupiah.Abstrak: Staphylococcus merupakan penyebab terjadinya infeksi. Infeksi dapat ditularkan dari suatu sumber dengan mekanisme tidak langsung melalui fomite. Uang kertas dapat bertindak sebagai transmisi agens infeksius ,uang berperan sebagai fomite. Pecahan uang yang lebih kecil nilainya memiliki kontaminasi yang lebih tinggi. Penelitian ini bertujuan untuk menganalisis perbedaan cemaran bakteri Staphylococcus sp pada pecahan uang kertas Rp.2.000, 5.000, Rp.10.000 dan Rp.20.000 yang beredar di warung jalan Adi Sucipto kota Pontianak. Metode penelitian yang digunakan dalam penelitian berbentuk komperatif dan sampel pada penelitian ini adalah pecahan uang kertas rupiah dengan.teknik pengambilan sampel menggunakan purposive sampling. Pemeriksaan Staphylococcus sp pada pecahan uang kertas rupiah menggunakan metode rinse. Pada hasil penelitian pecahan uang kertas Rp.2.000 yang tercemar staphylococcus sp adalah 80%, pecahan uang kertas Rp.5.000 yang tercemar staphylococcus spadalah 70%, pecahan uang kertas Rp.10.000 dan Rp.20.000 yang tercemar staphylococcus spadalah 50%. Berdasarkan data dari hasil penelitian yang telah didapat dianalisis menggunakan uji statistik fisher exact, didapatkan hasil p (0,477) >α (0,05) yang diartikan sebagai H1 ditolak. Sehingga dapat disimpulkan tidak ada perbedaan cemaran bakteri staphylococcus sp pada pecahan uang kertas rupiah.

Characteristics of Physician Relocation Following Hurricane Katrina

2009 ◽  
Vol 95 (1) ◽  
pp. 6-12
Author(s):  
Kusuma Madamala ◽  
Claudia R. Campbell ◽  
Edbert B. Hsu ◽  
Yu-Hsiang Hsieh ◽  
James James
Keyword(s):  
Hurricane Katrina ◽  
Gulf Coast ◽  
General Medicine ◽  
The United States ◽  
Lessons Learned ◽  
Bivariate Analysis ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Factors Associated ◽  
The Impact

ABSTRACT Introduction: On Aug. 29, 2005, Hurricane Katrina made landfall along the Gulf Coast of the United States, resulting in the evacuation of more than 1.5 million people, including nearly 6000 physicians. This article examines the relocation patterns of physicians following the storm, determines the impact that the disaster had on their lives and practices, and identifies lessons learned. Methods: An Internet-based survey was conducted among licensed physicians reporting addresses within Federal Emergency Management Agency-designated disaster zones in Louisiana and Mississippi. Descriptive data analysis was used to describe respondent characteristics. Multivariate logistic regression was performed to identify the factors associated with physician nonreturn to original practice. For those remaining relocated out of state, bivariate analysis with x2 or Fisher exact test was used to determine factors associated with plans to return to original practice. Results: A total of 312 eligible responses were collected. Among disaster zone respondents, 85.6 percent lived in Louisiana and 14.4 percent resided in Mississippi before the hurricane struck. By spring 2006, 75.6 percent (n = 236) of the respondents had returned to their original homes, whereas 24.4 percent (n = 76) remained displaced. Factors associated with nonreturn to original employment included family or general medicine practice (OR 0.42, 95 percent CI 0.17–1.04; P = .059) and severe or complete damage to the workplace (OR 0.24, 95 percent CI 0.13–0.42; P &lt; .001). Conclusions: A sizeable proportion of physicians remain displaced after Hurricane Katrina, along with a lasting decrease in the number of physicians serving in the areas affected by the disaster. Programs designed to address identified physician needs in the aftermath of the storm may give confidence to displaced physicians to return.

scholarly journals E-health and health literacy of young adult Ukrainian female immigrants and Polish counterparts

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
Y Krasko ◽  
J Marianowska ◽  
M Duplaga
Keyword(s):  
Health Status ◽  
Health Literacy ◽  
Young Adult ◽  
Online Survey ◽  
Health Behaviours ◽  
Study Groups ◽  
University Education ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Ehealth Literacy

Abstract Background According to recent projections, even 10% of Polish gross domestic product is contributed by Ukrainian immigrants. There is also a considerable number of Ukrainians continuing university education in Poland. The level of health literacy in Ukrainian society has not been studied so far. The aim of the study was the comparison of health literacy (HL) and e-health literacy (eHL) of young adult Ukrainian (UA) women with their Polish (PL) counterparts Methods A snowball technique was used to recruit a sample of UA women working or studying in Poland to the Internet-based survey. The questionnaire used in the study consisted of the 16-item European HL Survey questionnaire (HLS-EU-16), eHealth Literacy Scale (eHEALS), the set of the questions asking about health behaviours (HB), self-assessment of health status (HS) and items exploring sociodemographic variables. For comparison, the data of an age-matched sample of 100 respondents was extracted from the online survey performed in a representative sample of PL women. Results The mean age (standard deviation, SD) of 57 UA respondents was 20.23 (1.78) years and in Polish sample 20.25 (1.79). HL did not differ between both groups (11.06 (4.22) vs 11.44 (4.34), respectively, p = 0.53), but eHL was significantly lower in UA group (25.91 (5.36) vs 28.17 (5.37), U Mann-Whitney test, p = 0.01). Only 58.5% of UA respondents vs 80.5% of PL ones assessed their HS as at least good (Fisher exact test, p &lt; 0.001). The rates of active smoking (34.6% vs. 35.0%, p = 0.55), using e-cigarettes (35.3% vs 34.0%, p = 0.99), frequent alcohol consumption (26.9% vs. 20%, p = 0.41), and intensive physical activity (49.0% vs. 38.0%, p = 0.22) did not differ between study groups. Conclusions Young UA women show lower eHL than PL counterparts. Although HL and HB in both groups did not differ significantly, UA respondents have assessed their HS much lower than PL participants. Key messages E-health literacy and self-assessed health status were significantly lower among young Ukrainian than among Polish women. Both groups did not differ for health literacy and health behaviours.

scholarly journals AB0009 ASSOCIATION OF STAT4 RS7574865, RUNX1 RS9979383, IL6 RS1800795, IL6R RS2228145, IL6R RS4845618 WITH SYSTEMIC LUPUS ERYTHEMATOSUS SUSCEPTIBILITY AND SOME LUPUS MANIFESTATIONS IN BELARUSIAN POPULATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1039.2-1040
Author(s):  
N. Dostanko ◽  
V. Yagur ◽  
R. Goncharova ◽  
E. Siniauskaya ◽  
T. Zybalova
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Diagnostic Odds Ratio ◽  
Protective Role ◽  
Fisher Exact Test ◽  
Systemic Lupus ◽  
Exact Test ◽  
American College Of Rheumatology ◽  
Healthy Donors ◽  
Significant Difference

Background:Systemic lupus erythematosus (SLE) has a significant genetic predisposition. Many genetic variants of susceptibility to SLE have been published and analyzed, but the clinical and functional significance of the various genotypes has not yet been clearly defined [1].Objectives:To estimate the association between some of non-HLA gene polymorphisms such as STAT4 rs7574865, RUNX1 rs9979383, IL6 rs1800795, IL6R rs2228145, IL6R rs4845618 and susceptibility to SLE in Belarusian population as well as some disease manifestations.Methods:We examined 383 healthy blood donors and 54 SLE patients (18-72 years old, median age 35) classified according to the 1997 American College of Rheumatology (ACR) revised classification criteria [2]. Deoxyribonucleic acid was extracted from peripheral blood samples by phenol-chloroform method. Genotyping was performed by real-time PCR with fluorescent probes. Differences of distribution of all the single nucleotide polymorphism (SNP) genotypes and their associations with secondary antiphospholipid syndrom (APS) and lupus arthritis were analyzed using Pearson χ2 (χ2) and two-way Fisher exact test (F, p2-t). Diagnostic odds ratio (dOR), likelihood ratio of positive (LR +) and negative (LR –) tests and corresponding 95% confidence intervals (CI) were also calculated.Results:We revealed significant difference in STAT4 rs7574865 genotypes in SLE patients and healthy donors (χ2=8,27, р=0,016) with significant increase of ТТ genotype frequency in SLE patients vs healthy donors (χ2=6.83 p=0.009; p2-t =0.020; dOR=3.78 (CI95% 1.36-10.55); LR+ =3.44 (CI95% 1.35-8.71); LR– =0.91 (CI95% 0.83-0.98)). Lupus arthritis was more common in risk TT-genotype SLE carriers than in other SLE patients (χ2=5.902 p=0.015; p2-t =0.027).We revealed significant increase of СТ genotype (RUNX1 rs9979383) in healthy donors vs SLE patients (χ2=4.14; p=0.042; dOR=0.53 (CI95% 0.29-0.98); LR+ =0.69 (CI95% 0.45-0.99); LR– =1.3 (CI95% 1.01-1,56)). Lupus arthritis was more common in SLE СТ-genotype carriers than in other SLE patients (χ2=4.66 p=0.031; p2-t =0.058).Significant differences in IL6 rs1800795, IL6R rs2228145 and IL6R rs4845618 genotypes distribution between studied groups were not found (χ2, p=0.427, p=0.559 and p=0.407, correspondingly) but GG-genotype (IL6 rs1800795) carriership in SLE patients was associated with increased APS frequency (χ2=4.45, p=0.035; dOR=0.19 (CI95% 0.04-0.9); LR+ =0.28 (CI95% 0.07-0.93); LR– =1.41 (CI95% 1.03-1.64).Conclusion:Our data suggest the susceptibility to SLE in ТТ genotype of STAT4 rs7574865 polymorphism, protective role of СТ genotype of RUNX1 rs9979383 for SLE and association between GG-genotype of IL6 rs1800795 and APS in SLE patients in Belarusian population. Lupus arthritis was associated with ТТ genotype of STAT4 rs7574865 and СТ genotype of RUNX1 rs9979383.References:[1]Chen L, Morris DL, Vyse TJ. Genetic advances in systemic lupus erythematosus: an update. Curr Opin Rheumatol 2017;29:423–33.[2]Hochberg MC. Updating the American College of Rheumatology Revised Criteria for the classification of Systemic Lupus Erythematosus. Arthritis Rheum 1997;40:1725.Disclosure of Interests:None declared

scholarly journals Synergistic effect of genetic polymorphisms in TLR6 and TLR10 genes on the risk of pulmonary tuberculosis in a Moldavian population

2021 ◽  
pp. 175342592110299
Author(s):  
Alexander Varzari ◽  
Igor V. Deyneko ◽  
Elena Tudor ◽  
Harald Grallert ◽  
Thomas Illig
Keyword(s):  
Pulmonary Tuberculosis ◽  
Interaction Analysis ◽  
P Value ◽  
Fisher Exact Test ◽  
Snp Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Exact Test ◽  
Pulmonary Tb ◽  
The Republic

Polymorphisms in genes that control immune function and regulation may influence susceptibility to pulmonary tuberculosis (TB). In this study, 14 polymorphisms in 12 key genes involved in the immune response ( VDR, MR1, TLR1, TLR2, TLR10, SLC11A1, IL1B, IL10, IFNG, TNF, IRAK1, and FOXP3) were tested for their association with pulmonary TB in 271 patients with TB and 251 community-matched controls from the Republic of Moldova. In addition, gene–gene interactions involved in TB susceptibility were analyzed for a total of 43 genetic loci. Single nucleotide polymorphism (SNP) analysis revealed a nominal association between TNF rs1800629 and pulmonary TB (Fisher exact test P = 0.01843). In the pairwise interaction analysis, the combination of the genotypes TLR6 rs5743810 GA and TLR10 rs11096957 GT was significantly associated with an increased genetic risk of pulmonary TB (OR = 2.48, 95% CI = 1.62–3.85; Fisher exact test P value = 1.5 × 10−5, significant after Bonferroni correction). In conclusion, the TLR6 rs5743810 and TLR10 rs11096957 two-locus interaction confers a significantly higher risk for pulmonary TB; due to its high frequency in the population, this SNP combination may serve as a novel biomarker for predicting TB susceptibility.

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