scholarly journals Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Melisa Intan Barliana ◽  
Arif Satria Wira Kusuma ◽  
Widya Norma Insani ◽  
Sofa Dewi Alfian ◽  
Ajeng Diantini ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Drug Transport ◽  
Population Data ◽  
Cross Sectional Study ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Hardy Weinberg Equilibrium ◽  
Tuberculosis Therapy ◽  
Genetic Profiles

Abstract Objective The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively. Result The frequency of alleles of each gene was analyzed by Hardy–Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.

scholarly journals Oestradiol metabolism and androgen receptor genotypes are associated with right ventricular function

2015 ◽  
Vol 47 (2) ◽  
pp. 553-563 ◽  
Author(s):  
Corey E. Ventetuolo ◽  
Nandita Mitra ◽  
Fei Wan ◽  
Ani Manichaikul ◽  
R. Graham Barr ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Right Ventricular ◽  
Serum Testosterone ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Tight Linkage Disequilibrium ◽  
The Relationship ◽  
Rv Function

Sex hormones are linked to right ventricular (RV) function, but the relationship between genetic variation in these pathways and RV function is unknown.We performed a cross-sectional study of 2761 genotyped adults without cardiovascular disease. The relationships between RV measures and single nucleotide polymorphisms (SNPs) in 10 candidate genes were assessed. Urinary oestradiol (E2) metabolites produced by cytochrome P4501B1 (CYP1B1) and serum testosterone were measured in women and men respectively.In African-American (AA) women, the CYP1B1 SNP rs162561 was associated with RV ejection fraction (RVEF), such that each copy of the A allele was associated with a 2.0% increase in RVEF. Haplotype analysis revealed associations with RVEF in AA (global p<7.2×10−6) and white (global p=0.05) women. In white subjects, higher E2 metabolite levels were associated with significantly higher RVEF. In men, androgen receptors SNPs (rs1337080; rs5918764) were significantly associated with all RV measures and modified the relationship between testosterone and RVEF.Genetic variation in E2 metabolism and androgen signalling was associated with RV morphology in a sex-specific manner. The CYP1B1 SNP identified is in tight linkage disequilibrium with SNPs associated with pulmonary hypertension and oncogenesis, suggesting these pathways may underpin sexual dimorphism in RV failure.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

scholarly journals Use of flexible bronchoscopy for rapid diagnosis of suspected tubercular cases in rural India

2009 ◽  
Vol 3 (11) ◽  
pp. 860-864 ◽  
Author(s):  
Sameer Singhal ◽  
Abhay M. Gaidhane ◽  
Nazli Khatib ◽  
Tripti Hrivastava ◽  
Sanjay Diwan ◽  
...  
Keyword(s):  
Diagnostic Yield ◽  
Correct Diagnosis ◽  
Positive Culture ◽  
Cross Sectional Study ◽  
Flexible Bronchoscopy ◽  
Special Importance ◽  
Cross Sectional ◽  
Tuberculosis Patients ◽  
Negative Sputum ◽  
Tuberculosis Therapy

Background: Reaching a correct diagnosis is a challenge for physicians treating any of the 30% to 50% of pulmonary tuberculosis patients who have negative sputum cultures or who present with no sputum.  Flexible bronchoscopy acquires special importance for these cases for whom empirical anti-tuberculosis therapy is the only option left. In our study we aimed to assess the diagnostic yield of flexible bronchoscopy in patients, suspected to have tuberculosis, whose sputum smears were negative. Methodology: In our hospital-based cross-sectional study, 42 patients were enrolled by consecutive sampling. Flexible bronchoscopy and selective bronchial washings were done in all patients.  Results: Bronchoscopy lavage smears were positive for M. tuberculosis in 10 (23.8%) patients. Fifteen (35.7%) patients had positive culture. Conclusion: Flexible bronchoscopy has an important role in the diagnosis of patients suspected to have tuberculosis, whose sputum smears are negative or who can not produce sputum.

scholarly journals Effect of psychiatric co-morbidity on adherence to anti tubercular treatment: a cross sectional study from North India

2021 ◽  
Vol 8 (3) ◽  
pp. 1325
Author(s):  
Ravdeep Kaur ◽  
Tarundeep Singh ◽  
Shubh Mohan Singh ◽  
Rajesh Kumar
Keyword(s):  
Depressive Disorder ◽  
Cross Sectional Study ◽  
North India ◽  
Directly Observed Therapy ◽  
Cross Sectional ◽  
Tuberculosis Patients ◽  
Short Course ◽  
Co Morbidity ◽  
Mdr Tb ◽  
Tuberculosis Therapy

Background: Study explores relationship between depressive disorder and adherence to DOTS (Directly Observed Therapy Short Course) and whether treatment of depressive disorder according to severity of depressive disorder should be an option to improve adherence to DOTS.Methods: Study included 182 newly diagnosed adult cases of tuberculosis who were on anti- tuberculosis therapy (ATT) as per program guidelines and were in third month under DOTS category I and category II therapy. Patients were screened for depressive and anxiety disorder using PHQ-9 and GAD-7. Modified ACTG baseline questionnaire was used to collect data about adherence and reasons for partial adherence.Results: Overall prevalence of depressive disorder amongst participants was found to be 37.9% and that of partial adherence (missed two or more than two doses) was 12.1%. Partial adherence was mostly seen in the first month, followed by third and second month of DOTS. Twenty- two percent patients with depressive disorder were partially adherent to ATT. Odds ratio suggests higher risk being partially adherent to ATT were greater in the participants who had depressive disorder.Conclusions: This study highlights the benefit of screening patients while diagnosing tuberculosis patients for depressive disorder, to improve disease outcome and reduce likelihood of MDR-TB.

scholarly journals Impact of the Neuregulin rs35753505 C/T Polymorphisms on Neuregulin 1 Levels in Preterm Infants

2019 ◽  
Vol 7 (12) ◽  
pp. 1931-1934
Author(s):  
Bugis Mardina Lubis ◽  
Sjarif Hidajat Effendi ◽  
Ratna Akbari Ganie ◽  
Oke Rina Ramayani
Keyword(s):  
Preterm Infants ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Cross Sectional ◽  
Neuregulin 1 ◽  
Organ Systems ◽  
The Impact

BACKGROUND: Neuregulin (NRG) 1 plays an important role in the development of various organ systems in human. Single nucleotide polymorphisms rs35753505 C/Tof the gene encoding NRG1 evident as allele C and T with genotypes of CT, CC, and TT are believed to have an impact on NRG1 levels.AIM: To determine the impact of the NRGrs35753505 C/T polymorphisms on NRG1 levels in preterm infants.METHODS: A cross-sectional study was conducted from February to December 2018, whereas 48 eligible preterm infants with a gestational age of 32- < 37 weeks were enrolled. An umbilical cord blood specimen was collected for determination of NRG1 levels with enzyme-linked immunosorbent assay (ELISA) and NRG1 polymorphisms with polymerase chain reaction (PCR). Statistical analysis was performed with 95%CI and P value of < 0.05 was considered statistically significant.RESULTS: Median value of NRG1 levels (174.4 pg/ml) served as a cut off value. NRG 1 polymorphisms composed distribution of CC (31%), CT (42%), TT (27%) genotypes and distribution of C and T alleles were 52% and 48%. The median NRG1 levels in CC and CT genotypes were significantly lower compared to TT genotype (151.1 pg/ml vs 407.2 pg/ml, P = 0.005 and 159.1 pg/ml vs 407.2 pg/ml, P = 0.009). Subjects with C allele had significantly lower median NRG1 levels than T allele (151.1 pg/ml vs 407.2 pg/ml, P = 0.002). Subjects with CC and CT genotypes had higher risk to develop lower NRG1 levels compared to TT genotype (OR = 8.25, P = 0.016 and OR = 10.74, P = 0.005, respectively).CONCLUSION: Allele C is associated with lower NRG1 levels. Preterm infants with CC and CT genotypes pose a higher risk to have lower NRG1 levels.

The Prevalence of Ultrarapid Metabolizers of Codeine in a Diverse Urban Population

2018 ◽  
Vol 160 (3) ◽  
pp. 420-425
Author(s):  
Jordan Virbalas ◽  
Bernice E. Morrow ◽  
David Reynolds ◽  
John P. Bent ◽  
Thomas J. Ow
Keyword(s):  
New York ◽  
Census Data ◽  
Tertiary Care ◽  
Copy Number Variants ◽  
Ethnically Diverse ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Ultrarapid Metabolizers ◽  
Clinically Significant

Objective To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community. Study Design Cross-sectional study. Setting A tertiary care academic children’s hospital in the Bronx, New York. Subjects and Methods In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants’ haplotype. Results Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8%) identified as Hispanic or Latino. A total of 154 children (80.6%) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42%) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37%) were intermediate metabolizers. Only 3 children in our cohort (1.57%) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3% and 11.2%, respectively) with extensive variability within subpopulations. Conclusions The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.

Possible association between craniofacial dimensions and genetic markers in ESR1 and ESR2

2020 ◽  
Vol 47 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Marjorie Ayumi Omori ◽  
Jennifer Tsi Gerber ◽  
Guido Artemio Marañón-Vásquez ◽  
Mirian Aiko Nakane Matsumoto ◽  
Suyany Gabriely Weiss ◽  
...  
Keyword(s):  
Genetic Markers ◽  
Cross Sectional Study ◽  
Chi Square ◽  
Cross Sectional ◽  
Lateral Cephalograms ◽  
Mandibular Body ◽  
Chi Square Test ◽  
Hardy Weinberg Equilibrium ◽  
Polymerase Chain ◽  
School Of Dentistry

Objective: To investigate the association of genetic markers in ESR1 and ESR2 with craniofacial measurements. Design: Cross-sectional study. Setting: School of Dentistry of Ribeirão Preto, University of São Paulo. Participants: A total of 146 biologically unrelated, self-reported Caucasian Brazilians with no syndromic conditions were included. Methods: Sagittal and vertical measurements (ANB, S-N, Ptm’-A’, Co-Gn, Go-Pg, N-Me, ANS-Me, S-Go and Co-Go) from lateral cephalograms were examined for craniofacial evaluation. DNA was extracted from saliva and genetic markers in ESR1 (rs2234693 and rs9340799) and in ESR2 (rs1256049 and rs4986938) were analysed by real-time polymerase chain reaction. Hardy–Weinberg equilibrium was evaluated using the Chi-square test within each marker. The associations between craniofacial dimensions and genotypes were analysed by linear regression and adjusted by sex and age. The established alpha was 5%. Results: Individuals carrying CC in ESR1 rs2234693 had a decrease of –3.146 mm in ANS-Me ( P = 0.044). In addition, rs4986938 in ESR2 was associated with S-N measurement ( P = 0.009/ ß = –3.465). This marker was also associated with Go-Pg measurement, in which the CC genotype had a decrease of –3.925 mm in the length of the mandibular body ( P = 0.043). Conclusion: The present study suggests that in ESR1 and ESR2 are markers for variations in the craniofacial dimensions. However, further research should confirm the results.

Stress sensitization to depression following childhood adversity: Moderation by HPA axis and serotonergic multilocus profile scores

2020 ◽  
pp. 1-15
Author(s):  
Lisa R. Starr ◽  
Catherine B. Stroud ◽  
Zoey A. Shaw ◽  
Suzanne Vrshek-Schallhorn
Keyword(s):  
Genetic Variation ◽  
Life Events ◽  
Hpa Axis ◽  
Life Stress ◽  
Childhood Adversity ◽  
Risk Scores ◽  
Genetic Profile ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Stress Sensitization

Abstract Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic–pituitary–adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a “gene-by-environment-by-environment” interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.

The Pharmacogenetics and Inhibitor Risk (PIR) Study: Establishing the Spectrum of Factor (F)VIII Gene (F8) Mutations in African-American Hemophilia A Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3207-3207
Author(s):  
Tom E. Howard ◽  
Deepa K. Machiah ◽  
Kevin R. Viel ◽  
Cynthia Channel ◽  
Afshin Ameri ◽  
...  
Keyword(s):  
African American ◽  
Neutralizing Antibodies ◽  
Hemophilia A ◽  
Alternative Hypothesis ◽  
Cross Sectional Study ◽  
Causative Mutation ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Molecular Abnormalities ◽  
Ethnic Subgroups

Abstract The development of neutralizing antibodies against plasma-derived or recombinant (r) molecules of wildtype (wt) factor (F)VIII protein is the most serious complication of replacement therapy for hemophilia A (hA) patients. Although the pathogenesis of these antibodies, termed inhibitors, is complex and poorly understood, ethnicity, a recently established risk determinant, is clearly involved since African-American (AA) patients experience this complication ~2-fold more often than Caucasians. In a previous study -- in which the FVIII genes (F8) from 137 unrelated healthy people, representing 7 ethnic groups, were resequenced -- we identified 4 common nonsynonymous single nucleotide polymorphisms (nsSNPs) and thereby demonstrated that FVIII is not a monomorphic protein in non-hemophiliacs. Interestingly, 5 of the 6 distinct wt proteins encoded by the allelic combinations or haplotypes (H) of these nsSNPs, designated H1, H2, ..., H5, are expressed by AA’s compared to only 2 in Caucasians (H1 and H2). Because H3, H4 and H5 are 1) partially defined by AA-restricted minor alleles of R484H and M2238V, 2 nsSNPs that substitute amino acids in the A2 and C2 major B-cell inhibitor epitopes, 2) represent the wt FVIII protein in ~27% of AA’s, and 3) differ from the rFVIII proteins used clinically, we designed the PIR study -- the 1st cross-sectional study of AA hA patients -- to determine if pharmacogenetic factors contribute to their greater inhibitor risk. Because the strongest known risk factor for inhibitors is the F8 mutation type, we are resequencing the known functional regions of F8 in the 1st 50 enrolled PIR subjects, out of the 223 total AA hA patients treated at the six participating Region IV South hemophilia treatment centers, to test the plausible alternative hypothesis that the higher inhibitor incidence is due to a different spectrum of molecular abnormalities than has been found in other ethnic subgroups of patients already examined at the DNA sequence level. We have 1) determined the plasma FVIII-activity and -antigen levels, 2) identified the causative mutation in 18 patients, several of which are novel, and 3) are currently performing RT-PCR analyses for detecting the common inversions in introns 1 and 22. Once completed, we will statistically compare the prevalence of AA F8 mutation subtypes to that in hA patients from other ethnic subgroups (detailed in the HAMSTeRS database), and the proportion of AA FVIII deficiencies that are 1) severe, moderate and mild, and 2) CRM-positive and -negative.

Sign in / Sign up

Export Citation Format

Share Document