CYP2B6 Non-Coding Variation Associated with Smoking Cessation Is Also Associated with Differences in Allelic Expression, Splicing, and Nicotine Metabolism Independent of Common Amino-Acid Changes
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{"title"=>"CYP2B6 non-coding variation associated with smoking cessation is also associated with differences in allelic expression, splicing, and nicotine metabolism independent of common amino-acid changes", "type"=>"journal", "authors"=>[{"first_name"=>"A. Joseph", "last_name"=>"Bloom", "scopus_author_id"=>"22933440900"}, {"first_name"=>"Maribel", "last_name"=>"Martinez", "scopus_author_id"=>"7404593589"}, {"first_name"=>"Li Shiun", "last_name"=>"Chen", "scopus_author_id"=>"7409440955"}, {"first_name"=>"Laura J.", "last_name"=>"Bierut", "scopus_author_id"=>"6701374894"}, {"first_name"=>"Sharon E.", "last_name"=>"Murphy", "scopus_author_id"=>"7402779008"}, {"first_name"=>"Alison", "last_name"=>"Goate", "scopus_author_id"=>"7006308333"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84896697913", "sgr"=>"84896697913", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24260284", "doi"=>"10.1371/journal.pone.0079700", "pui"=>"372403525"}, "id"=>"665f0516-ee81-3ffb-afd1-53206d6ea20e", "abstract"=>"The Cytochrome P450 2B6 (CYP2B6) enzyme makes a small contribution to hepatic nicotine metabolism relative to CYP2A6, but CYP2B6 is the primary enzyme responsible for metabolism of the smoking cessation drug bupropion. Using CYP2A6 genotype as a covariate, we find that a non-coding polymorphism in CYP2B6 previously associated with smoking cessation (rs8109525) is also significantly associated with nicotine metabolism. The association is independent of the well-studied non-synonymous variants rs3211371, rs3745274, and rs2279343 (CYP2B6*5 and *6). Expression studies demonstrate that rs8109525 is also associated with differences in CYP2B6 mRNA expression in liver biopsy samples. Splicing assays demonstrate that specific splice forms of CYP2B6 are associated with haplotypes defined by variants including rs3745274 and rs8109525. These results indicate differences in mRNA expression and splicing as potential molecular mechanisms by which non-coding variation in CYP2B6 may affect enzymatic activity leading to differences in metabolism and smoking cessation.", "link"=>"http://www.mendeley.com/research/cyp2b6-noncoding-variation-associated-smoking-cessation-also-associated-differences-allelic-expressi", "reader_count"=>7, "reader_count_by_academic_status"=>{"Student > Master"=>5, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Student > Master"=>5, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1283914"], "description"=>"<p>Numbers refer to pairwise R<sup>2</sup>.</p>", "links"=>[], "tags"=>["locus", "snps", "genotyped", "cogend", "metabolism"], "article_id"=>853190, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LD_structure_of_the_CYP2A6_CYP2B6_locus_for_common_SNPs_genotyped_in_the_COGEND_metabolism_study_/853190", "title"=>"LD structure of the <i>CYP2A6/CYP2B6</i> locus for common SNPs genotyped in the COGEND metabolism study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283915"], "description"=>"<p>Samples, excluding rs2279343 heterozygotes, are either heterozygous (CT) at rs8100458 (C/*5, n = 5), or rs8100458 TT homozygotes (T/*5, n = 4). ΔCt differs significantly by genotype (p = 0.025). Relative expression, ΔCt, was determined by subtracting the smaller Ct value of one allele PCR reaction from the larger Ct value of the other allele PCR reaction normalized against the average ratio obtained from gDNAs for each genotype. The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p>", "links"=>[], "tags"=>["allele-specific", "cdnas", "rs3211371", "heterozygous", "biopsy"], "article_id"=>853191, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_allele_specific_gene_expression_Ct_for_cDNAs_from_rs3211371_CYP2B6_5_heterozygous_liver_biopsy_samples_/853191", "title"=>"The ratio of allele-specific gene expression (ΔCt) for cDNAs from rs3211371 (<i>CYP2B6*5</i>) heterozygous liver biopsy samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283916"], "description"=>"<p>Samples, excluding rs3211371 heterozygotes, are either heterozygous (CT) at rs8100458 (C/*6, n = 15) or rs8100458 TT homozygotes (T/*6, n = 19). ΔCt differs significantly by genotype (p = 2.4×10<sup>−6</sup>). Relative expression, ΔCt, was determined by subtracting the smaller Ct value of one allele PCR reaction from the larger Ct value of the other allele PCR reaction normalized against the average ratio obtained from gDNAs for each genotype. The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p>", "links"=>[], "tags"=>["allele-specific", "cdnas", "rs2279343", "heterozygous", "biopsy"], "article_id"=>853192, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_allele_specific_gene_expression_Ct_for_cDNAs_from_rs2279343_CYP2B6_6_heterozygous_liver_biopsy_samples_/853192", "title"=>"The ratio of allele-specific gene expression (ΔCt) for cDNAs from rs2279343 (<i>CYP2B6*6</i>) heterozygous liver biopsy samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283917"], "description"=>"<p>Splice form nomenclature follows prior literature <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone.0079700-Hofmann1\" target=\"_blank\">[27]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone.0079700-Lamba1\" target=\"_blank\">[28]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone.0079700-Miles1\" target=\"_blank\">[38]</a>. The locations of common non-synonymous variants are marked on the full-length transcript. Not to scale.</p>", "links"=>[], "tags"=>["locations", "primers", "quantitative", "Real-time", "splice-form"], "article_id"=>853193, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Common_CYP2B6_splice_forms_and_the_relative_locations_of_primers_used_in_quantitative_real_time_splice_form_expression_assays_/853193", "title"=>"Common <i>CYP2B6</i> splice-forms, and the relative locations of primers used in quantitative real-time splice-form expression assays.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283918"], "description"=>"<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) genotype, as dictated by the optimum model predicting ΔCt (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t003\" target=\"_blank\">Table 3</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘6/7F’ and ‘7R’ from the Ct value of the PCR reaction using primers ‘3/7F’ and ‘7R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p>", "links"=>[], "tags"=>["aberrant", "exon", "3-7", "splicing", "sv1", "6-7"], "article_id"=>853194, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_aberrant_exon_3_7_splicing_generating_the_SV1_splice_form_to_correct_exon_6_7_splicing_/853194", "title"=>"The ratio of aberrant exon 3-7 splicing (generating the SV1 splice-form) to correct exon 6-7 splicing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283919"], "description"=>"<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) and rs3786552 genotype, as dictated by the optimum model predicting ΔCt (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t004\" target=\"_blank\">Table 4</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘2/3F’ and ‘4R’ from the Ct value of the PCR reaction using primers ‘2/3F’ and ‘3/3AB R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p>", "links"=>[], "tags"=>["aberrant", "exon", "splicing", "sv2-5", "transcripts", "exons"], "article_id"=>853195, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_aberrant_exon_3_3A_B_splicing_generating_the_SV2_5_splice_forms_to_all_transcripts_that_include_exons_2_3_amp_4_/853195", "title"=>"The ratio of aberrant exon 3-3A/B splicing (generating the SV2-5 splice-forms) to all transcripts that include exons 2, 3 & 4.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283920"], "description"=>"<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) and rs3786552 genotype, as dictated by the optimum model predicting ΔCt (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t005\" target=\"_blank\">Table 5</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘2/3F’ and ‘4R’ from the Ct value of the PCR reaction using primers ‘2/3F’ and ‘3/5R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range.</p>", "links"=>[], "tags"=>["aberrant", "exon", "3-5", "splicing", "sv7-8", "transcripts", "exons"], "article_id"=>853196, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_aberrant_exon_3_5_splicing_generating_the_SV7_8_splice_forms_to_all_transcripts_that_include_exons_2_3_amp_4_/853196", "title"=>"The ratio of aberrant exon 3-5 splicing (generating the SV7-8 splice-forms) to all transcripts that include exons 2, 3 & 4.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283921"], "description"=>"<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) genotype, as dictated by the optimum model predicting ΔCt (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t006\" target=\"_blank\">Table 6</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/9F’ and ‘9R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p>", "links"=>[], "tags"=>["aberrant", "exon", "7-9", "splicing", "7-8"], "article_id"=>853197, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_aberrant_exon_7_9_splicing_generating_the_SV9_955_MP1_splice_forms_to_correct_exon_7_8_splicing_/853197", "title"=>"The ratio of aberrant exon 7-9 splicing (generating the SV9/λMP1 splice-forms) to correct exon 7-8 splicing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283922"], "description"=>"<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) genotype, as dictated by the optimum model predicting ΔCt (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t007\" target=\"_blank\">Table 7</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/8A F’ and ‘9R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p>", "links"=>[], "tags"=>["aberrant", "exon", "7-8a", "splicing", "7-8"], "article_id"=>853198, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ratio_of_aberrant_exon_7_8A_splicing_generating_the_955_MP8_splice_form_to_correct_exon_7_8_splicing_/853198", "title"=>"The ratio of aberrant exon 7-8A splicing (generating the λMP8 splice-form) to correct exon 7-8 splicing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283923"], "description"=>"<p>Polymorphic sites analyzed are given at the top of each column by rs number, gene position and further relevant description. Haplotypes are ordered by common allele name and frequency in the COGEND metabolism dataset.</p>", "links"=>[], "tags"=>["haplotypes", "metabolism"], "article_id"=>853199, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_haplotypes_in_metabolism_experiment_/853199", "title"=>"<i>CYP2B6</i> haplotypes in metabolism experiment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283924"], "description"=>"a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘6/7F’ and ‘7R’ from the Ct value of the PCR reaction using primers ‘3/7F’ and ‘7R’ (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004\" target=\"_blank\">Figure 4</a>, primer sequences in table S4).</p>", "links"=>[], "tags"=>["variants", "predicting", "aberrant", "exon", "splicing", "exons", "generating", "sv1", "individually", "optimum", "multivariate"], "article_id"=>853200, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_variants_predicting_aberrant_exon_3_7_splicing_skipping_exons_4_6_generating_the_SV1_splice_form_versus_correct_exon_6_7_splicing_individually_or_in_an_optimum_multivariate_model_/853200", "title"=>"<i>CYP2B6</i> variants predicting aberrant exon 3−7 splicing (skipping exons 4−6), generating the SV1 splice-form, versus correct exon 6−7 splicing, individually or in an optimum multivariate model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283925"], "description"=>"a<p>the probability that the parameter estimate is different by chance from the reference, i.e. all <i>CYP2A6</i> (n = 271) and <i>CYP2B6</i> (n = 126) alleles not included in the multivariate regression. All <i>CYP2A6</i> alleles presented are loss-of-function alleles associated with reduced metabolism (−) relative to the reference <i>CYP2A6</i> alleles; all <i>CYP2B6</i> alleles presented are associated with increased metabolism (+) relative to the reference (rs8109525G) <i>CYP2B6</i> alleles. rs8109525 is in high linkage disequilibrium with rs8100458 (R<sup>2</sup>>0.95).</p>", "links"=>[], "tags"=>["haplotypes", "multivariate", "regression"], "article_id"=>853201, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_haplotypes_associated_with_D_2_cotinine_D_2_cotinine_D_2_nicotine_in_a_multivariate_regression_model_with_CYP2A6_haplotypes_/853201", "title"=>"<i>CYP2B6</i> haplotypes associated with D<sub>2</sub>cotinine/(D<sub>2</sub>cotinine+ D<sub>2</sub>nicotine) in a multivariate regression model with <i>CYP2A6</i> haplotypes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283926"], "description"=>"a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘2/3F’ and ‘4R’ from the Ct value of the PCR reaction using primers ‘2/3F’ and ‘3/5R’ (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004\" target=\"_blank\">Figure 4</a>, primer sequences in table S4).</p>", "links"=>[], "tags"=>["variants", "predicting", "aberrant", "exon", "3-5", "generating", "sv7-8", "transcripts", "exons", "individually", "optimum", "multivariate"], "article_id"=>853202, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_variants_predicting_aberrant_exon_3_5_splicing_generating_the_SV7_8_splice_forms_versus_all_transcripts_that_include_exons_2_3_4_individually_or_in_an_optimum_multivariate_model_/853202", "title"=>"<i>CYP2B6</i> variants predicting aberrant exon 3-5 splicing, generating the SV7-8 splice-forms, versus all transcripts that include exons 2, 3 & 4, individually or in an optimum multivariate model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283927"], "description"=>"a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘2/3F’ and ‘4R’ from the Ct value of the PCR reaction using primers ‘2/3F’ and ‘3/3AB R’ (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004\" target=\"_blank\">Figure 4</a>, primer sequences in table S4).</p>", "links"=>[], "tags"=>["variants", "predicting", "aberrant", "exon", "generating", "sv2-5", "transcripts", "exons", "individually", "optimum", "multivariate"], "article_id"=>853203, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_variants_predicting_aberrant_exon_3_3A_B_splicing_generating_the_SV2_5_splice_forms_versus_all_transcripts_that_include_exons_2_3_4_individually_or_in_an_optimum_multivariate_model_/853203", "title"=>"<i>CYP2B6</i> variants predicting aberrant exon 3-3A/B splicing, generating the SV2-5 splice-forms, versus all transcripts that include exons 2, 3 & 4, individually or in an optimum multivariate model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283928"], "description"=>"a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/8A F’ and ‘9R’ (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004\" target=\"_blank\">Figure 4</a>, primer sequences in table S4).</p>", "links"=>[], "tags"=>["variants", "predicting", "aberrant", "exon", "7-8a", "generating", "7-8", "individually", "optimum", "multivariate"], "article_id"=>853204, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_variants_predicting_aberrant_exon_7_8A_splicing_generating_the_MP8_splice_form_versus_correct_exon_7_8_splicing_individually_or_in_an_optimum_multivariate_model_/853204", "title"=>"<i>CYP2B6</i> variants predicting aberrant exon 7-8A splicing, generating the λMP8 splice-form, versus correct exon 7-8 splicing, individually or in an optimum multivariate model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283929"], "description"=>"a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/9F’ and ‘9R’ (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004\" target=\"_blank\">Figure 4</a>, primer sequences in table S4).</p>", "links"=>[], "tags"=>["variants", "predicting", "aberrant", "exon", "7-9", "generating", "sv9", "7-8", "individually", "optimum", "multivariate"], "article_id"=>853205, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.t006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_variants_predicting_aberrant_exon_7_9_splicing_generating_the_SV9_and_MP1_splice_forms_versus_correct_exon_7_8_splicing_individually_or_in_an_optimum_multivariate_model_/853205", "title"=>"<i>CYP2B6</i> variants predicting aberrant exon 7-9 splicing, generating the SV9 and λMP1 splice-forms, versus correct exon 7-8 splicing, individually or in an optimum multivariate model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-15 03:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1283930", "https://ndownloader.figshare.com/files/1283931", "https://ndownloader.figshare.com/files/1283932", "https://ndownloader.figshare.com/files/1283933"], "description"=>"<div><p>The Cytochrome P450 2B6 (CYP2B6) enzyme makes a small contribution to hepatic nicotine metabolism relative to CYP2A6, but CYP2B6 is the primary enzyme responsible for metabolism of the smoking cessation drug bupropion. Using <i>CYP2A6</i> genotype as a covariate, we find that a non-coding polymorphism in <i>CYP2B6</i> previously associated with smoking cessation (rs8109525) is also significantly associated with nicotine metabolism. The association is independent of the well-studied non-synonymous variants rs3211371, rs3745274, and rs2279343 (<i>CYP2B6*5</i> and <i>*6</i>). Expression studies demonstrate that rs8109525 is also associated with differences in <i>CYP2B6</i> mRNA expression in liver biopsy samples. Splicing assays demonstrate that specific splice forms of <i>CYP2B6</i> are associated with haplotypes defined by variants including rs3745274 and rs8109525. These results indicate differences in mRNA expression and splicing as potential molecular mechanisms by which non-coding variation in <i>CYP2B6</i> may affect enzymatic activity leading to differences in metabolism and smoking cessation.</p></div>", "links"=>[], "tags"=>["non-coding", "smoking", "cessation", "differences", "allelic", "nicotine", "metabolism", "amino-acid"], "article_id"=>853206, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["A. Joseph Bloom", "Maribel Martinez", "Li-Shiun Chen", "Laura J. Bierut", "Sharon E. Murphy", "Alison Goate"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0079700.s001", "https://dx.doi.org/10.1371/journal.pone.0079700.s002", "https://dx.doi.org/10.1371/journal.pone.0079700.s003", "https://dx.doi.org/10.1371/journal.pone.0079700.s004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CYP2B6_Non_Coding_Variation_Associated_with_Smoking_Cessation_Is_Also_Associated_with_Differences_in_Allelic_Expression_Splicing_and_Nicotine_Metabolism_Independent_of_Common_Amino_Acid_Changes/853206", "title"=>"<i>CYP2B6</i> Non-Coding Variation Associated with Smoking Cessation Is Also Associated with Differences in Allelic Expression, Splicing, and Nicotine Metabolism Independent of Common Amino-Acid Changes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-11-15 03:01:27"}

PMC Usage Stats | Further Information

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Relative Metric

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