Pharmacogenetics and genomics最新文献

{"title":"Influence of MDR1 gene polymorphism (2677G>T) on expression and function of P-glycoprotein at the blood-brain barrier: utilizing novel P-glycoprotein humanized mice with mutation.","authors":"Yuki Yamasaki,&nbsp;Takashi Moriwaki,&nbsp;Seiryo Ogata,&nbsp;Shingo Ito,&nbsp;Sumio Ohtsuki,&nbsp;Genki Minegishi,&nbsp;Satoshi Abe,&nbsp;Yumi Ohta,&nbsp;Kanako Kazuki,&nbsp;Kaoru Kobayashi,&nbsp;Yasuhiro Kazuki","doi":"10.1097/FPC.0000000000000481","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000481","url":null,"abstract":"<p><p>P-glycoprotein, the encoded product of the MDR1 / ABCB1 gene in humans, is expressed in numerous tissues including brain capillary endothelial cells and restricts the distribution of xenobiotics into the brain as an efflux pump. Although a large number of single nucleotide polymorphisms in the MDR1 gene have been identified, the influence of the nonsynonymous 2677G>T/A single nucleotide polymorphism on P-glycoprotein at the blood-brain barrier has remained unclear. In the present study, we developed a novel P-glycoprotein humanized mouse line carrying the 2677G>T mutation by utilizing a mouse artificial chromosome vector constructed by genetic engineering technology and we evaluated the influence of 2677G>T on the expression and function of P-glycoprotein at the blood-brain barrier in vivo . The results of this study showed that the introduction of the 2677G>T mutation does not alter the expression levels of P-glycoprotein protein in the brain capillary fraction. On the other hand, the brain penetration of verapamil, a representative substrate of P-glycoprotein, was increased by the introduction of the 2677G>T mutation. These results suggested that the 2677G>T single nucleotide polymorphism may attenuate the function of P-glycoprotein, resulting in increased brain penetration of P-glycoprotein substrates, without altering the expression levels of P-glycoprotein protein in the blood-brain barrier. This mutant mouse line is a useful model for elucidating the influence of an MDR1 gene single nucleotide polymorphism on the expression and function of P-glycoprotein at the blood-brain barrier.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 8","pages":"288-292"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10544110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attitudes on pharmacogenomic results as secondary findings among medical geneticists.","authors":"Meghan N Bartos,&nbsp;Stuart A Scott,&nbsp;Ethylin Wang Jabs,&nbsp;Hetanshi Naik","doi":"10.1097/FPC.0000000000000479","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000479","url":null,"abstract":"<p><strong>Objectives: </strong>As evidence mounts supporting the utility of pharmacogenomic-guided medication management, incorporating pharmacogenomic genes into secondary finding results from sequencing panels is increasingly under consideration. We studied medical geneticists' attitudes on receiving pharmacogenomic results as secondary finding.</p><p><strong>Methods: </strong>Four focus groups with 16 medical geneticists total were conducted followed by thematic analysis.</p><p><strong>Results: </strong>All participants ordered genetic sequencing tests; however, the majority had rarely or never ordered pharmacogenomic tests (10/16) or prescribed medications with established response variability (11/16). In total 81.3% expressed low comfort interpreting pharmacogenomic results without appropriate clinical resources (13/16). The positives of receiving pharmacogenomic results as secondary finding included prevention of adverse drug reactions in adults, grateful information-seeking patients, the ability to rapidly prescribe more effective treatments and appreciation of the recent advances in both pharmacogenomic knowledge and available guidelines. Negatives included laboratory reporting issues, exclusivity of pharmacogenomic results to certain populations, lengthy reports concealing pharmacogenomic results in patient charts and laboratories marketing to individuals without prior pharmacogenomic knowledge or targeting inappropriate populations. The most desirable pharmacogenomic resources included a universal electronic health record clinical decision support tool to assist identifying and implementing pharmacogenomic results, a specialized pharmacist as part of the care team, additional pharmacogenomic training during medical/graduate school, and a succinct interpretation of pharmacogenomic results included on laboratory reports.</p><p><strong>Conclusions: </strong>The majority of participants agreed that adding certain actionable pharmacogenomic genes to the American College of Medical Genetics and Genomics SF list is reasonable; however, this was qualified with a need for additional resources to support implementation.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 8","pages":"273-280"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10189825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of ATP8B3 gene polymorphisms with aspirin-exacerbated respiratory disease in asthmatics.","authors":"Jong-Uk Lee,&nbsp;Min Kyung Kim,&nbsp;Seung-Lee Park,&nbsp;Da Jeong Bae,&nbsp;Hun Soo Chang,&nbsp;Choon-Sik Park,&nbsp;Jong Sook Park","doi":"10.1097/FPC.0000000000000480","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000480","url":null,"abstract":"<p><strong>Background: </strong>Aspirin-exacerbated respiratory disease (AERD), an asthma phenotype, often presents with severe manifestations and it remains widely underdiagnosed because of insufficient awareness of the relationship between the ingestion of nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid (ASA), and asthma exacerbation. Our previous genome-wide association study demonstrated an association between a single nucleotide polymorphism (SNP) of the ATP8B3 gene and the risk of AERD. This study examined AERD-related SNPs of the ATP8B3 gene in a large population.</p><p><strong>Methods: </strong>Twenty-five SNPs of ATP8B3 were genotyped with the GoldenGate assay using VeraCode microbeads in 141 asthmatics with AERD and 995 Aspirin-tolerant asthma (ATA). The genotype distribution was analyzed using logistic regression models. The declines in forced expiratory volume in 1 second (FEV1)following an ASA challenge were compared among the genotypes and haplotypes using a type III generalized linear model.</p><p><strong>Results: </strong>The minor allele frequencies (MAFs) of rs10421558 A>G in the 5'UTR and rs10403288 G>A in the intron were significantly lower in the AERD than the ATA [34.0% vs. 43.8%, OR = 0.66 (0.62-0.92), Pcorr = 0.03 and 28.4% vs. 35.4%, OR = 0.62 (0.59-0.89), Pcorr = 0.016, respectively]. BL1ht5 was significantly higher in the AERD [7.6% vs. 1.6%, OR = 12.23 (0.2-0.51), P = 4.7 × 10 -4 , Pcorr = 0.001]. Among them, rs10421558 A>G and BL1ht5 were associated with the percent decline in FEV1 on the oral ASA challenge test.</p><p><strong>Conclusion: </strong>The minor allele of rs10421558 A>G in the 5'UTR may protect against the development of AERD via the increased production of ATP8B3.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 8","pages":"281-287"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10563096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis.","authors":"Ying Zhang,&nbsp;Xu Hao,&nbsp;Kelu Hou,&nbsp;Lei Hu,&nbsp;Jingyuan Shang,&nbsp;Shiyu He,&nbsp;Changqing Yang,&nbsp;Lin Huang,&nbsp;Yufei Feng","doi":"10.1097/FPC.0000000000000470","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000470","url":null,"abstract":"<p><strong>Objective: </strong>To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole.</p><p><strong>Methods: </strong>We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to 18 March 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity, and neurotoxicity.</p><p><strong>Results: </strong>A total of 20 studies were included. Intermediate metabolizers (IMs) and poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) [risk ratio (RR), 1.18; 95% confidence interval (CI), 1.03-1.34; I2 = 0%; P = 0.02; RR, 1.28; 95% CI, 1.06-1.54; I2 = 0%; P = 0.01]. PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR, 2.18; 95% CI, 1.35-3.53; I2 = 0%; P = 0.001; RR, 1.80; 95% CI, 1.23-2.64; I2 = 0%; P = 0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR, 1.60; 95% CI, 0.94-2.74; I2 = 27%; P = 0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity.</p><p><strong>Conclusion: </strong>IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deserves clinical attention.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"257-267"},"PeriodicalIF":2.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40682758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of pharmacologic interactions between omeprazole and tacrolimus in a membranous nephropathy patient with CYP3A5 nonexpresser: a case report.","authors":"Yanli Li,&nbsp;Yi Liu,&nbsp;Zengxian Sun","doi":"10.1097/FPC.0000000000000478","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000478","url":null,"abstract":"<p><p>Tacrolimus has been widely used in membranous nephropathy in recent years. The drug interactions of the coadministration of tacrolimus with omeprazole in CYP3A5 nonexpresser membranous nephropathy patients have not been demonstrated. Here, we report an idiopathic membranous nephropathy patient who was with CYP2C19*2/*2, CYP3A5*3/*3 (nonexpresser) and ABCB1 (3435 TT, 1236 computed tomography, 2677 TT) genotype requiring treatment with tacrolimus and omeprazole and found to have fluctuating metabolism of tacrolimus. This study shows that tacrolimus and omeprazole have pharmacologic drug interactions in CYP3A5 nonexpressers, implying that the CYP3A and ABCB1 gene mutations linked to tacrolimus metabolism may alter tacrolimus levels in the blood. The observed concentrations of tacrolimus were decreased after the discontinuation of omeprazole therapy. It demonstrates that, in addition to genotype, clinical covariates, such as omeprazole are important when it comes to better understanding and prediction of tacrolimus dosage. It is deemed necessary to monitor tacrolimus blood concentrations and make dose adjustments when patients were coadministered with omeprazole.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 7","pages":"268-271"},"PeriodicalIF":2.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10582991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of anti-TNF-α treatment with gut microbiota of patients with ankylosing spondylitis.","authors":"Qinghong Dai,&nbsp;Xuyang Xia,&nbsp;Chenjia He,&nbsp;Yupeng Huang,&nbsp;Yidan Chen,&nbsp;Yang Wu,&nbsp;Yuehong Chen,&nbsp;Qianqian Hou,&nbsp;Yang Shu,&nbsp;Wei Zhang,&nbsp;Heng Xu,&nbsp;Geng Yin,&nbsp;Qibing Xie","doi":"10.1097/FPC.0000000000000468","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000468","url":null,"abstract":"<p><strong>Objective: </strong>Gut dysbiosis contributes to multiple autoimmune diseases, including ankylosing spondylitis, which is commonly treated with tumor necrosis factor (TNF)-α inhibitors (TNFis). Because host TNF-α levels are considered to interact with gut microbiota, we aimed to systematically investigate the microbiota profile of ankylosing spondylitis patients with anti-TNF-α-based treatment and identify potential key bacteria.</p><p><strong>Methods: </strong>Fecal samples were collected from 11 healthy controls and 24 ankylosing spondylitis patients before/after anti-TNF-α treatment, the microbiota profiles of which were evaluated by 16S ribosomal DNA amplicon sequencing and subsequent bioinformatic analysis.</p><p><strong>Results: </strong>Significantly different microbial compositions were observed in samples from ankylosing spondylitis patients compared with healthy controls, characterized by a lower abundance of short-chain fatty acid (SCFA)-producing bacteria. All patients exhibited a positive response after anti-TNF-α treatment, accompanied by a trend of restoration in the microbiota compositions and functional profile of ankylosing spondylitis patients to healthy controls. In particular, the abundance of SCFA-producing bacteria (e.g. Megamonsa and Lachnoclostridium ) was not only significantly lower in ankylosing spondylitis patients than in healthy controls and restored after anti-TNF-α treatment but also negatively correlated with disease severity (e.g. cor  = -0.52, P  = 8 × 10 -5 for Megamonsa ). In contrast, Bacilli and Haemophilus may contribute to ankylosing spondylitis onset and severity.</p><p><strong>Conclusions: </strong>Microbiota dysbiosis in ankylosing spondylitis patients can be restored after anti-TNF-α treatment, possibly by impacting SCFA-producing bacteria.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 7","pages":"247-256"},"PeriodicalIF":2.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/0d/pgen-32-247.PMC9351697.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10225607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer genomic medicine in Japan and the roles of pharmacists.","authors":"Tohru Aomori,&nbsp;Hiroomi Sakurai,&nbsp;Hiroshi Nishihara","doi":"10.1097/FPC.0000000000000476","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000476","url":null,"abstract":"<p><p>Cancer genomic medicine (CGM) is a medical service that provides optimized treatment for each patient based on genes, biomarkers, environment, and lifestyle. In Japan, the approval of designed core hospitals for CGM started in 2017. In June 2019, two types of cancer gene panel tests became available in the national health insurance system, and CGM was socially implemented. While CGM is still in its infancy and there are some issues that need to be resolved, there are cases where the treatment has shown dramatic results. The present review highlights the CGM system in Japan, the issues it faces, and the role of pharmacists in this system.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 6","pages":"242-245"},"PeriodicalIF":2.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10543655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetic analysis of canonical versus noncanonical pathway of NF-kB in Crohn's disease patients under anti-tumor necrosis factor-α treatment.","authors":"Eleana F Stavrou,&nbsp;Fani Chatzopoulou,&nbsp;Charalabos Antonatos,&nbsp;Panagiota Pappa,&nbsp;Eutychia Makridou,&nbsp;Konstantinos Oikonomou,&nbsp;Andreas Kapsoritakis,&nbsp;Petros S Potamianos,&nbsp;Konstantinos Karmiris,&nbsp;Charalambos Tzathas,&nbsp;Dimitris Chatzidimitriou,&nbsp;Ioannis S Vizirianakis,&nbsp;Yiannis Vasilopoulos","doi":"10.1097/FPC.0000000000000471","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000471","url":null,"abstract":"<p><strong>Objectives: </strong>This study explores the potential of gene polymorphisms in the canonical and noncanonical NF-kB signaling pathway as a prediction biomarker of anti-tumor necrosis factor (TNF)α response in Crohn's patients.</p><p><strong>Materials and methods: </strong>A total of 109 Greek patients with Crohn's disease (CD) were recruited, and the genotype of TLR2 rs3804099, LTA rs909253, TLR4 rs5030728, and MAP3K14/NIK rs7222094 single nucleotide polymorphisms was investigated for association with response to anti-TNFα therapy. Patient's response to therapy was based on the Crohn's Disease Activity Index, depicting the maximum response within 24 months after initiation of treatment.</p><p><strong>Results: </strong>Seventy-three patients (66.7%) were classified as responders while 36 as nonresponders (33.3%). Comparing allelic frequencies between responders and nonresponders, the presence of TLR2 rs3804099 T allele was associated with nonresponse (P = 0.003), even after stratification by anti-TNFα drugs (infliximab: P = 0.032, adalimumab: P = 0.026). No other association was identified for the rest of the polymorphisms under study. Haplotype analysis further enhanced the association of rs3804099 T allele with loss of response, even though the results were NS (P = 0.073).</p><p><strong>Conclusion: </strong>Our results suggest that polymorphisms in the canonical NF-kB pathway genes could potentially act as a predictive biomarker of anti-TNFα response in CD.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 6","pages":"235-241"},"PeriodicalIF":2.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide DNA methylation profile of peripheral blood lymphocytes from subjects with nonsteroidal anti-inflammatory drug-induced respiratory diseases.","authors":"Jong-Uk Lee,&nbsp;Hun Soo Chang,&nbsp;Min Kyung Kim,&nbsp;Seung-Lee Park,&nbsp;Jung Hyun Kim,&nbsp;Jong-Sook Park,&nbsp;Choon-Sik Park","doi":"10.1097/FPC.0000000000000475","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000475","url":null,"abstract":"<p><strong>Background: </strong>Significant changes in CpG methylation have been identified in nasal polyps, which are the main targets of nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD); however, these polyps are composed of various cellular components. In the present study, whole-genome CpG methylation in peripheral blood lymphocytes (PBLs) was analyzed to define the epigenetic changes in lymphocytes, which are the primary immune cells involved in NERD.</p><p><strong>Materials and methods: </strong>Genomic DNA from peripheral blood mononuclear cells from 27 NERD and 24 aspirin-tolerant asthma (ATA) was subjected to bisulfate conversion and a methylation array. Quantitative CpG methylation, the β-values as a quantitative measure of DNA methylation, in lymphocytes were calculated after adjustments for cellular composition.</p><p><strong>Results: </strong>Fifty-six hypermethylated and three hypomethylated differentially methylated CpGs (DMCs) in PBLs in the NERD compared with ATA. The top 10 CpG loci predicted the methylation risk score, with a positive predictive value of 91.3%, a negative predictive value of 81.5% and an accuracy of 84.3%. As demonstrated in the nasal polyps, 30 DMCs were predicted to bind to the following 10 transcription factors, ranked in descending order: AP-2alphaA, TFII-1, STAT4, FOXP3, GR, c-Est-1, E2F-1, XBP1, ENKTF-1 and NF-1. Gene ontology analysis identified 13 categories such as regulation of T-helper 17 cell differentiation, including SMAD7 and NFKBIZ. PBLs in NERD contained no DMCs in genes associated with the prostaglandin and leukotriene pathways, which were found in ATA.</p><p><strong>Conclusion: </strong>PBLs in NERD form a unique pattern of DNA CpG methylation, and the combined analysis may provide predictive values for NERD.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 6","pages":"226-234"},"PeriodicalIF":2.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10543653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen.","authors":"Yaya Kassogue, Brehima Diakite, Mamoudou Maiga, Oumar Kassogue, Issa Konate, Kadidiatou Tamboura, Fousseyni Diarra, Zoumana Diarra, Mahamadou Karamoko Sawadogo, Yaya Goita, Sidi Boula Sissoko, Adama Seydou Sissoko, Nouhoum Guirou, Hind Dehbi, Sellama Nadifi, Sekou Bah, Cheick Bougadari Traore, Bakarou Kamate, Sounkalo Dao, Guimogo Dolo","doi":"10.1097/FPC.0000000000000477","DOIUrl":"10.1097/FPC.0000000000000477","url":null,"abstract":"<p><strong>Objectives: </strong>The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study.</p><p><strong>Patients and methods: </strong>Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays.</p><p><strong>Results: </strong>The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274.</p><p><strong>Conclusion: </strong>Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 6","pages":"219-225"},"PeriodicalIF":1.7,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613628/pdf/EMS146401.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}