scholarly journals Classification of small ruminant lentivirus subtype A2, subgroups 1 and 2 based on whole genome comparisons and complex recombination patterns

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 1449
Author(s):  
Aaron M. Dickey ◽  
Timothy P. L. Smith ◽  
Michael L. Clawson ◽  
Michael P. Heaton ◽  
Aspen M. Workman
Keyword(s):  
Small Ruminant ◽  
Transmembrane Protein ◽  
Full Length ◽  
Nucleotide Polymorphisms ◽  
Wasting Disease ◽  
Single Nucleotide ◽  
Viral Genomes ◽  
Haplotype 1 ◽  
Genome Scale

Background: Small ruminant lentiviruses (SRLVs) cause a multisystemic chronic wasting disease in sheep across much of the world. SRLV subtype A2 is prevalent in North America and further classified into multiple subgroups based on variation in the group antigens gene (gag) and envelope (env) genes. In sheep, the ovine transmembrane protein 154 (TMEM154) gene is associated with SRLV susceptibility. Ewes with at least one copy of TMEM154 encoding a full-length protein with glutamate at position 35 (E35; haplotypes 2 and 3), are highly susceptible to SRLV infection while ewes with any combination of TMEM154 haplotypes which encodes lysine (K35; haplotype 1), or truncated proteins (haplotypes 4 and 6) are several times less so. A2 subgroups 1 and 2 are associated with host TMEM154 genotypes; subgroup 1 with the K35/K35 genotype and subgroup 2 with the E35/E35 genotype. Methods:  Sequence variation within and among full-length assemblies of SRLV subtype A2 subgroups 1 and 2 was analyzed to identify genome-scale recombination patterns and subgroup-specific variants. Results:  Consensus viral genomes were assembled from 23 infected sheep, including animals of assorted TMEM154 genotypes comprised of haplotypes 1, 2, or 3. Viral genome analysis identified viral subgroups 1 and 2 among the samples, and revealed additional sub-structure within subgroup 2 based on models predicting complex patterns of recombination between the two subgroups in several genomes. Animals with evidence of dual subgroup infection also possessed the most diverse quasi-species and the most highly recombined consensus genomes. After accounting for recombination, 413 subgroup diagnostic single nucleotide polymorphisms (SNPs) were identified. Conclusions:  The viral subgroup framework developed to classify SRLV consensus genomes along a continuum of recombination suggests that animals with the TMEM154 E35/K35 genotype may represent a reservoir for producing viral genomes representing recombination between A2 subgroups 1 and 2.

scholarly journals Classification of small ruminant lentivirus subtype A2, subgroups 1 and 2 based on whole genome comparisons and complex recombination patterns

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1449
Author(s):  
Aaron M. Dickey ◽  
Timothy P. L. Smith ◽  
Michael L. Clawson ◽  
Michael P. Heaton ◽  
Aspen M. Workman
Keyword(s):  
Sequence Variation ◽  
Small Ruminant ◽  
Transmembrane Protein ◽  
Full Length ◽  
Wasting Disease ◽  
Viral Genomes ◽  
Haplotype 1 ◽  
Genome Scale ◽  
Genome Comparisons

Background: Small ruminant lentiviruses (SRLVs) cause a multisystemic chronic wasting disease in sheep across much of the world. SRLV subtype A2 is prevalent in North America and further classified into multiple subgroups based on variation in the group antigens gene (gag) and envelope (env) genes. In sheep, the ovine transmembrane protein 154 (TMEM154) gene is associated with SRLV susceptibility. Ewes with at least one copy of TMEM154 encoding a full-length protein with glutamate at position 35 (E35; haplotypes 2 and 3), are highly susceptible to SRLV infection while ewes with any combination of TMEM154 haplotypes which encodes lysine (K35; haplotype 1), or truncated proteins (haplotypes 4 and 6) are several times less so. A2 subgroups 1 and 2 are associated with host TMEM154 genotypes; subgroup 1 with the K35/K35 genotype and subgroup 2 with the E35/E35 genotype. Methods: The goals of this study were to analyze sequence variation within and among SRLV subtype A2 subgroups 1 and 2 and to identify genome-scale recombination patterns. This was done using full-length assemblies of virus samples. Results: Consensus viral genomes were assembled for 23 infected sheep, including animals of assorted TMEM154 genotypes comprised of haplotypes 1, 2, or 3. Viral genome analysis identified viral subgroups 1 and 2 among the samples, and revealed additional sub-structure within subgroup 2 based on models predicting complex patterns of recombination between the two subgroups in several genomes. Animals with evidence of dual subgroup infection also possessed the most diverse quasi-species and the most highly recombined genomes. Conclusions: The viral subgroup framework developed to classify SRLV consensus genomes along a continuum of recombination suggests that animals with the TMEM154 E35/K35 genotype may represent a reservoir for producing viral genomes representing recombination between A2 subgroups 1 and 2.

Variation at the von Willebrand Factor (vWF) Gene Locus Is Associated With Plasma vWF:Ag Levels: Identification of Three Novel Single Nucleotide Polymorphisms in the vWF Gene Promoter

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4277-4283 ◽  
Author(s):  
Angela M. Keightley ◽  
Y. Miu Lam ◽  
Jolene N. Brady ◽  
Cherie L. Cameron ◽  
David Lillicrap
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Von Willebrand Factor ◽  
Gene Locus ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Polymorphic Variation ◽  
Single Nucleotide ◽  
Haplotype 1 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5′-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40.6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P = .008; Kruskal-Wallis test,P = .006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects > 40 years of age (analysis of variance [ANOVA], P = .003; Kruskal-Wallis test, P= .001), but was not maintained for subjects ≤ 40 years of age (ANOVA, P > .4; Kruskal-Wallis test, P > .4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFκB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFκB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.

DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3692-3700 ◽  
Author(s):  
Stéphanie Dulucq ◽  
Geneviève St-Onge ◽  
Vincent Gagné ◽  
Marc Ansari ◽  
Daniel Sinnett ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Lymphoblastic Leukemia ◽  
Luciferase Expression ◽  
Nucleotide Polymorphisms ◽  
Promoter Polymorphisms ◽  
Single Nucleotide ◽  
Childhood All ◽  
Reductase Gene ◽  
Haplotype 1 ◽  
Folate Cycle

Abstract Dihydrofolate reductase (DHFR) is the major target of methotrexate (MTX), a key component in childhood acute lymphoblastic leukemia (ALL) treatment. A total of 15 polymorphisms in DHFR promoter were analyzed, and 3 sites (C−1610G/T, C−680A, and A−317G) were identified as sufficient to define observed haplotypes (tag single nucleotide polymorphisms [tagSNPs]). These polymorphisms were investigated for association with treatment response in 277 children with ALL. Lower event-free survival (EFS) was associated with homozygosity for the allele A−317 and C−1610 (P = .03 and .02), and with the haplotype *1, defined by both C−1610 and A−317 alleles (P = .03). The haplotype *1 conferred higher transcriptional activity (P < .01 compared with haplotypes generating minimal luciferase expression). Quantitative mRNA analysis showed higher DHFR levels for particular haplotype *1 carriers (P < .01). The analysis combining haplotype *1 with thymidylate synthase (TS) and cyclin D1 (CCND1) genotypes previously shown to affect ALL outcome showed that the number of event-predisposing genotypes was associated with increasingly lower EFS (P < .001). In conclusion, DHFR promoter polymorphisms are associated with worse ALL outcome, likely due to a higher DHFR expression. Combined effects among genes of the folate cycle can further accentuate differences in the response to the treatment.

Classification of wheat PPO genes and effect of non-synonymous cSNP on kernel PPO activity

2008 ◽  
Vol 5 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Wang Xiao-Bo ◽  
Ma Chuan-Xi ◽  
Si Hong-Qi ◽  
He Xian-Fang
Keyword(s):  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Chain Reaction ◽  
Wheat Varieties ◽  
Single Nucleotide ◽  
Pcr Product ◽  
Dnaman Software ◽  
Dna Fragment ◽  
Polymerase Chain

AbstractPolyphenol oxidase (PPO) activity is highly related to the undesirable browning of wheat-based end products. In this study, wheat PPO sequences (mRNA) were searched/BLASTed in the NCBI database and aligned using DNAMAN software. The results showed that wheat PPO genes could be divided into two clusters (I and II) and that three genes (‘i’) of cluster II seemed not to be located on chromosomes 2A and 2D. Ninety-four single nucleotide polymorphisms (SNPs) were detected between two haplotypes of the PPO gene on chromosome 2D. Eighty of these were found in the coding region (coding (c) SNPs) and 36 were non-synonymous cSNPs, which could affect the PPO amino acid sequence. Primers (STS-H) were designed at some non-synonymous cSNPs sites and were used to investigate the correlations between allelic variants and PPO activity of seeds – a total of 130 common wheat varieties were evaluated in 2 years. The results showed that STS-H could amplify a 460 bp DNA fragment in most cultivars with high PPO activity, while no PCR product was detected in most cultivars with low PPO activity. To improve the selection efficiency of a single dominance molecular marker, the multiplex polymerase chain reaction (PCR) system of STS-H and STS01 markers was also studied, based on the complementary between them.

scholarly journals No Association between Single Nucleotide Polymorphisms (SNPs) of the Interferon-Induced Transmembrane Protein 3 (IFITM3) Gene and the Susceptibility of Alzheimer’s Disease (AD)

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 55
Author(s):  
Sae-Young Won ◽  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Nucleotide Polymorphisms ◽  
Neurodegenerative Disorder ◽  
Transmembrane Protein ◽  
Haplotype Frequency ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Frequency Distributions ◽  
First Case

Background and Objectives: Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder, characterized by the accumulation of amyloid-beta (Aβ) in the brain. A recent study reported that the interferon-induced transmembrane protein 3 (IFITM3) protein plays a pivotal role in Aβ processing by the γ-secretase complex. Since several single nucleotide polymorphisms (SNPs) of the IFITM3 gene are related to the function and expression levels of the IFITM3 gene, the relationship between genetic polymorphisms in the IFITM3 gene and susceptibility to AD needs to be investigated. Materials and Methods: We investigated the genotype and allele frequencies of IFITM3 polymorphisms in 177 AD patients and 233 matched healthy controls by amplicon sequencing. In addition, we compared the genotype, allele and haplotype frequencies between AD patients and matched controls and performed an association analysis. Results: There were no significant differences in the genotype, allele or haplotype frequency distributions of the IFITM3 polymorphisms between AD patients and matched controls. Conclusions: To the best of our knowledge, this is the first case-control association study of the IFITM3 gene in AD.

scholarly journals Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality

2021 ◽  
Vol 12 ◽  
Author(s):  
Marie-Christine Bartens ◽  
Amanda J. Gibson ◽  
Graham J. Etherington ◽  
Federica Di Palma ◽  
Angela Holder ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Bos Indicus ◽  
Full Length ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Brown Swiss ◽  
Cattle Breeds ◽  
Species Specific ◽  
Mycobacterial Antigens

Recent evidence suggests that several cattle breeds may be more resistant to infection with the zoonotic pathogen Mycobacterium bovis. Our data presented here suggests that the response to mycobacterial antigens varies in macrophages generated from Brown Swiss (BS) and Holstein Friesian (HF) cattle, two breeds belonging to the Bos taurus family. Whole genome sequencing of the Brown Swiss genome identified several potential candidate genes, in particular Toll-like Receptor-2 (TLR2), a pattern recognition receptor (PRR) that has previously been described to be involved in mycobacterial recognition. Further investigation revealed single nucleotide polymorphisms (SNP) in TLR2 that were identified between DNA isolated from cells of BS and HF cows. Interestingly, one specific SNP, H326Q, showed a different genotype frequency in two cattle subspecies, Bos (B.) taurus and Bos indicus. Cloning of the TLR2 gene and subsequent gene-reporter and chemokine assays revealed that this SNP, present in BS and Bos indicus breeds, resulted in a significantly higher response to mycobacterial antigens as well as tri-acylated lipopeptide ligands in general. Comparing wild-type and H326Q containing TLR2 responses, wild-type bovine TLR2 response showed clear, diminished mycobacterial antigen responses compared to human TLR2, however bovine TLR2 responses containing H326Q were found to be partially recovered compared to human TLR2. The creation of human:bovine TLR2 chimeras increased the response to mycobacterial antigens compared to the full-length bovine TLR2, but significantly reduced the response compared to the full-length human TLR2. Thus, our data, not only present evidence that TLR2 is a major PRR in the mammalian species-specific response to mycobacterial antigens, but furthermore, that there are clear differences between the response seen in different cattle breeds, which may contribute to their enhanced or reduced susceptibility to mycobacterial infection.

scholarly journals Towards Understanding of Polymorphism of the G-rich Region of Human Papillomavirus Type 52

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1294 ◽  
Author(s):  
Maja Marušič ◽  
Janez Plavec
Keyword(s):  
Human Papillomavirus ◽  
Snp Analysis ◽  
Nucleotide Polymorphisms ◽  
Structural Elements ◽  
Structural Polymorphism ◽  
Single Nucleotide ◽  
Viral Genomes ◽  
Guanine Residue ◽  
G Quadruplex ◽  
Domains Of Life

The potential to affect gene expression via G-quadruplex stabilization has been extended to all domains of life, including viruses. Here, we investigate the polymorphism and structures of G-quadruplexes of the human papillomavirus type 52 with UV, CD and NMR spectroscopy and gel electrophoresis. We show that oligonucleotide with five G-tracts folds into several structures and that naturally occurring single nucleotide polymorphisms (SNPs) have profound effects on the structural polymorphism in the context of G-quadruplex forming propensity, conformational heterogeneity and folding stability. With help of SNP analysis, we were able to select one of the predominant forms, formed by G-rich sequence d(G3TAG3CAG4ACACAG3T). This oligonucleotide termed HPV52(1–4) adopts a three G-quartet snap back (3 + 1) type scaffold with four syn guanine residues, two edgewise loops spanning the same groove, a no-residue V loop and a propeller type loop. The first guanine residue is incorporated in the central G-quartet and all four-guanine residues from G4 stretch are included in the three quartet G-quadruplex core. Modification studies identified several structural elements that are important for stabilization of the described G-quadruplex fold. Our results expand set of G-rich targets in viral genomes and address the fundamental questions regarding folding of G-rich sequences.

Variation at the von Willebrand Factor (vWF) Gene Locus Is Associated With Plasma vWF:Ag Levels: Identification of Three Novel Single Nucleotide Polymorphisms in the vWF Gene Promoter

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4277-4283 ◽  
Author(s):  
Angela M. Keightley ◽  
Y. Miu Lam ◽  
Jolene N. Brady ◽  
Cherie L. Cameron ◽  
David Lillicrap
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Von Willebrand Factor ◽  
Gene Locus ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Polymorphic Variation ◽  
Single Nucleotide ◽  
Haplotype 1 ◽  
Von Willebrand ◽  
Willebrand Factor

Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5′-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40.6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P = .008; Kruskal-Wallis test,P = .006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects > 40 years of age (analysis of variance [ANOVA], P = .003; Kruskal-Wallis test, P= .001), but was not maintained for subjects ≤ 40 years of age (ANOVA, P > .4; Kruskal-Wallis test, P > .4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFκB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFκB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.

scholarly journals CYP2B618492T→C Polymorphism Compromises Efavirenz Concentration in Coinfected HIV and Tuberculosis Patients CarryingCYP2B6Haplotype *1/*1

2014 ◽  
Vol 58 (4) ◽  
pp. 2268-2273 ◽  
Author(s):  
Weerawat Manosuthi ◽  
Chonlaphat Sukasem ◽  
Supeda Thongyen ◽  
Samruay Nilkamhang ◽  
Sukanya Manosuthi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Body Weight ◽  
Standard Deviation ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Tuberculosis Patients ◽  
Hiv Rna ◽  
Haplotype 1 ◽  
To Receive

ABSTRACTData regarding the effect of theCYP2B618492T→C polymorphism on plasma efavirenz concentrations and 96-week virologic responses in patients coinfected with HIV and tuberculosis (TB) are still unavailable. A total of 139 antiretroviral-naive HIV-infected adults with active TB were prospectively enrolled to receive efavirenz 600 mg-tenofovir 300 mg-lamivudine 300 mg. Eight single nucleotide polymorphisms (SNPs) withinCYP2B6were genotyped. Seven SNPs, including 64C→T, 499C→G, 516G→T, 785A→G, 1375A→G, 1459C→T, and 21563C→T, were included forCYP2B6haplotype determination. TheCYP2B618492T→C polymorphism was studied in 48 patients who carried haplotype *1/*1. At 12 and 24 weeks after antiretroviral therapy, plasma efavirenz concentrations at 12 h after dosing were measured. Plasma HIV RNA was monitored every 12 weeks for 96 weeks. Of 48 patients {body weight [mean ± standard deviation (SD)], 56 ± 10 kg}, 77% received a rifampin-containing anti-TB regimen. No drug resistance-associated mutation was detected at baseline. The frequencies of the wild type (18492TT) and the heterozygous (18492TC) and homozygous (18492CC) mutants of theCYP2B618492T→C polymorphism were 39%, 42%, and 19%, respectively. At 12 weeks, mean (±SD) efavirenz concentrations of patients who carried the 18492TT, 18492TC, and 18492CC mutants were 2.8 ± 1.6, 1.7 ± 0.9, and 1.4 ± 0.5 mg/liter, respectively (P= 0.005). At 24 weeks, the efavirenz concentrations of the corresponding groups were 2.4 ± 0.8, 1.7 ± 0.8, and 1.2 ± 0.4 mg/liter, respectively (P= 0.003). A low efavirenz concentration was independently associated with 18492T→C (β = −0.937,P= 0.004) and high body weight (β = −0.032,P= 0.046). At 96 weeks, 19%, 17%, and 28% of patients carrying the 18492TT, 18492TC, and 18492CC mutants, respectively, had plasma HIV RNA levels of >40 copies/ml and developed efavirenz-associated mutations (P= 0.254). In summary, theCYP2B618492T→C polymorphism compromises efavirenz concentrations in patients who carryCYP2B6haplotype *1/*1 and are coinfected with HIV and tuberculosis.

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