Pharmacogenetics and genomics最新文献

{"title":"Association between opioid and dopamine receptor gene polymorphisms OPRM1 rs1799971, DAT VNTR 9-10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 and alcohol dependence: an ethnicity oriented meta-analysis.","authors":"Navina Suresh,&nbsp;Suvarna Jyothi Kantipudi,&nbsp;Deepika Ramu,&nbsp;Suresh Kumar Muniratnam,&nbsp;Vettriselvi Venkatesan","doi":"10.1097/FPC.0000000000000502","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000502","url":null,"abstract":"<p><strong>Objective: </strong>We carried out a meta-analysis of four opioid and dopamine candidate gene polymorphisms having conflicting results in prior literature, namely OPRM1 rs1799971, DAT VNTR 9-10 repeat, DRD1 rs4532 and DRD2 rs1799732, to clarify their association with alcohol dependence and further stratified results by ethnicity to analyze possible ethnicity-mediated effects.</p><p><strong>Methods: </strong>Inclusion criteria: case-control studies assessing the association between OPRM1 rs1799971, DAT VNTR 9/10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 with alcohol dependence, with sufficient data available to calculate the odds ratio (OR) within a 95% confidence interval. Exclusion criteria: studies of quantitative measures of alcohol consumption, response to medications or analyses of other markers in the candidate genes, studies without controls, animal studies and lack of genotyping data. Information sources were PubMed, Google Scholar and ScienceDirect databases, all of which were searched for articles published till 2021. Heterogeneity between studies and publication bias, subgroup analyses and sensitivity analyses were carried out.</p><p><strong>Results: </strong>A total of 41 published studies were included in the current meta-analysis. For the OPRM1 gene, there was a statistically significant association in the Asian population with a pooled OR of 1.707 (95% CI, 1.32-2.20 P  < 0.0001) and 1.618 (95% CI, 1.16-2.26 P  = 0.005) in the additive and dominant genetic models. For DAT VNTR 9/10 repeat, a statistically significant association of the risk vs. common allele was observed in AD with a pooled OR of 1.104 (95% CI, 1.00-1.21 P  = 0.046) in the allele model and the additive genetic model in the Caucasian population with pooled OR of 1.152 (95% CI, 1.01-1.31 P  = 0.034).</p><p><strong>Conclusion: </strong>Results indicate that some of the effects may be ethnicity-specific.</p><p><strong>Other: </strong>The meta-analysis has been registered in the CRD PROSPERO (CRD42023411576).</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 7","pages":"139-152"},"PeriodicalIF":2.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318439","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":"Real-world pharmacogenetics of statin intolerance: effects of SLCO1B1, ABCG2 , and CYP2C9 variants.","authors":"K Ivar Lönnberg,&nbsp;Aleksi Tornio,&nbsp;Päivi Hirvensalo,&nbsp;Jenni Keskitalo,&nbsp;Anna-Liina Mustaniemi,&nbsp;Johanna I Kiiski,&nbsp;Anne M Filppula,&nbsp;Mikko Niemi","doi":"10.1097/FPC.0000000000000504","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000504","url":null,"abstract":"<p><strong>Objective: </strong>The association of SLCO1B1 c.521T>C with simvastatin-induced muscle toxicity is well characterized. However, different statins are subject to metabolism and transport also by other proteins exhibiting clinically meaningful genetic variation. Our aim was to investigate associations of SLCO1B1 c.521T>C with intolerance to atorvastatin, fluvastatin, pravastatin, rosuvastatin, or simvastatin, those of ABCG2 c.421C>A with intolerance to atorvastatin, fluvastatin, or rosuvastatin, and that of CYP2C9*2 and *3 alleles with intolerance to fluvastatin.</p><p><strong>Methods: </strong>We studied the associations of these variants with statin intolerance in 2042 patients initiating statin therapy by combining genetic data from samples from the Helsinki Biobank to clinical chemistry and statin purchase data.</p><p><strong>Results: </strong>We confirmed the association of SLCO1B1 c.521C/C genotype with simvastatin intolerance both by using phenotype of switching initial statin to another as a marker of statin intolerance [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.08-3.25, P  = 0.025] and statin switching along with creatine kinase measurement (HR 5.44, 95% CI 1.49-19.9, P  = 0.011). No significant association was observed with atorvastatin and rosuvastatin. The sample sizes for fluvastatin and pravastatin were relatively small, but SLCO1B1 c.521T>C carriers had an increased risk of pravastatin intolerance defined by statin switching when compared to homozygous reference T/T genotype (HR 2.11, 95% CI 1.01-4.39, P  = 0.047).</p><p><strong>Conclusion: </strong>The current results can inform pharmacogenetic statin prescribing guidelines and show feasibility for the methodology to be used in larger future studies.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 7","pages":"153-160"},"PeriodicalIF":2.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9961588","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":"N -acetyltransferase 2 haplotype modifies risks for both dyslipidemia and urinary bladder cancer.","authors":"Kyung U Hong, David W Hein","doi":"10.1097/FPC.0000000000000500","DOIUrl":"10.1097/FPC.0000000000000500","url":null,"abstract":"<p><p>A novel haplotype in N -acetyltransferase 2 ( NAT2 ) composed of seven non-coding variants (rs1495741, rs4921913, rs4921914, rs4921915, rs146812806, rs35246381, and rs35570672) has been linked to dyslipidemia by multiple, independent genome-wide association studies. The haplotype is located approximately 14 kb downstream of NAT2-coding region (ch8:18,272,377-18,272,881; GRCh38/hg38) and represents a non-coding, intergenic haplotype. Interestingly, the same dyslipidemia NAT2 haplotype is also linked to urinary bladder cancer risk. Dyslipidemia risk alleles are associated with rapid acetylator phenotype, whereas bladder cancer risk alleles are associated with slow acetylator, suggesting that the level of systemic NAT2 activity modifies the risk of these pathologies. We speculate that rs1495741 (and its associated haplotype) belongs to a distal regulatory element of human NAT2 gene (e.g., enhancer or silencer), and the genetic variation at the newly discovered haplotype results in a differential level of NAT2 gene expression. Understanding how this NAT2 haplotype contributes to not only urinary bladder cancer but also to dyslipidemia will ultimately help devise strategies to identify and protect susceptible individuals.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 6","pages":"136-137"},"PeriodicalIF":1.7,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234326","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":"Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.","authors":"Nana Agyemang, Kimberly K Scarsi, Paxton Baker, Laura M Smeaton, Anthony T Podany, Maxine Olefsky, Elizabeth Woolley, Elizabeth Barr, Michelle Pham, Sajeeda Mawlana, Khuanchai Supparatpinyo, Sivaporn Gatechompol, Emilia M Jalil, Luis Gadama, Sharlaa Badal-Faesen, Marije Van Schalkwyk, Cecelia Kayama, Pablo F Belaunzaran-Zamudio, Catherine Godfrey, Susan E Cohn, Rosie Mngqibisa, David W Haas","doi":"10.1097/FPC.0000000000000501","DOIUrl":"10.1097/FPC.0000000000000501","url":null,"abstract":"<p><strong>Objective: </strong>In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions.</p><p><strong>Methods: </strong>Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters.</p><p><strong>Results: </strong>Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC 0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC 0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC 0-8h values similar to controls, while NAT2 slow acetylators had AUC 0-8h values 36% higher than controls.</p><p><strong>Conclusion: </strong>CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 6","pages":"126-135"},"PeriodicalIF":1.7,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/b4/pgen-33-126.PMC10309098.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10663642","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":"Bone marrow mesenchymal stem cell-derived exosomes carrying E3 ubiquitin ligase ITCH attenuated cardiomyocyte apoptosis by mediating apoptosis signal-regulated kinase-1.","authors":"Xuejun Li,&nbsp;Xuanyi Hu,&nbsp;Qiansu Chen,&nbsp;Tian Jiang","doi":"10.1097/FPC.0000000000000499","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000499","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have been verified to perform an effective role in treating acute myocardial infarction (MI). Herein, we aimed to investigate the role of BMSC-derived exosomes carrying itchy E3 ubiquitin ligase (ITCH) in MI and the underlying mechanism involved.</p><p><strong>Methods: </strong>BMSCs were isolated from rat bone marrow and exosomes were extracted using ultra-high speed centrifugation. Exosomes uptake by cardiomyoblasts was determined by PKH-67 staining. Rat cardiomyoblast cell line H9C2 was stimulated by hypoxia, as in vitro model. H9C2 cell apoptosis was determined by flow cytometry. Cell viability was examined by cell counting kit-8 assay. Western blotting was performed to determine the expression of ITCH, apoptosis signal-regulated kinase-1 (ASK1), and apoptotic-related protein cleaved-caspase 3 and Bcl-2. Ubiquitination assay was employed to measure the levels of ASK1 ubiquitination.</p><p><strong>Results: </strong>Exosomes derived from BMSCs were endocytosed by H9C2 cardiomyoblasts. BMSC-Exo downregulated cleaved-caspase 3 expression, upregulated Bcl-2 expression, further suppressed H9C2 cell apoptosis under hypoxia treatment, meanwhile the expression of ASK1 was downregulated, and similar effects were observed in BMSC-cultured supernatant (BMSC-S). However, these effects were reversed by exosome inhibitor GW4869. BMSC-derived exosomes enhanced ASK1 ubiquitination and degradation. Mechanically, exosomes of ITCH-knockdown BMSCs promoted H9C2 cell apoptosis and upregulated ASK1 expression. Overexpression of ITCH enhanced ASK1 ubiquitination and degradation. Further, the protein expression of ASK1 and cleaved-caspase 3 was upregulated and Bcl-2 protein expression was downregulated. ITCH-knockdown BMSC exosomes increased cardiomyoblast apoptosis.</p><p><strong>Conclusion: </strong>BMSC-derived exosomes carrying ITCH suppressed cardiomyoblast apoptosis, promoted cardiomyoblast viability, and improved myocardial injury in AMI by mediating ASK1 ubiquitination.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 6","pages":"117-125"},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234329","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":"Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans.","authors":"Somila Mateza, Yuki Bradford, Gary Maartens, Simiso Sokhela, Nomathemba C Chandiwana, Willem D F Venter, Frank A Post, Marylyn D Ritchie, David W Haas, Phumla Sinxadi","doi":"10.1097/FPC.0000000000000491","DOIUrl":"10.1097/FPC.0000000000000491","url":null,"abstract":"<p><strong>Objective: </strong>Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans.</p><p><strong>Methods: </strong>Genetic sub-study of adults randomized to initiate TAF or TDF together with dolutegravir and emtricitabine was conducted. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine β2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations.</p><p><strong>Results: </strong>336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 ( P  = 0.022), ABCC10 rs2125739 ( P  = 0.07), and ABCC4 rs1059751 ( P  = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 ( P  = 0.0013), rs691857 ( P  = 0.00039), and PKD2 rs72659631 ( P  = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 ( P  = 3.4 × 10 -9 ), CDH4 rs66494466 ( P  = 5.6 × 10 -8 ), and ITGA4 rs3770126 ( P  = 6.1 × 10 -7 ).</p><p><strong>Conclusion: </strong>Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 5","pages":"91-100"},"PeriodicalIF":1.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194046","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":"Cisplatin-induced ototoxicity: a novel approach to an ancient problem.","authors":"Nabil E Omar,&nbsp;Hazem Elewa","doi":"10.1097/FPC.0000000000000497","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000497","url":null,"abstract":"<p><p>With the scarcity of pharmacological otoprotective agents against cisplatin-induced ototoxicity (CIO), researchers find themselves compelled to look at and navigate all possible strategies to identify ways to prevent CIO. One of these promising strategies is pharmacogenomic implementation. This strategy aims for identifying and detecting high-risk genetic variants to tailor cisplatin therapy to reach the best survival outcomes with the least risk of ototoxicity.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 5","pages":"111-115"},"PeriodicalIF":2.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193613","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":"Mouse nerve growth factor suppresses neuronal apoptosis in valproic acid-induced autism spectrum disorder rats by regulating the phosphoinositide-3-kinase/serine/threonine kinase signaling pathway.","authors":"Jie Jian,&nbsp;Li-Guo Li,&nbsp;Peng-Ju Zhao,&nbsp;Rui-Juan Zheng,&nbsp;Xian-Wen Dong,&nbsp;Yong-Hong Zhao,&nbsp;Bao-Qi Yin,&nbsp;Sheng Li,&nbsp;Hui Cheng,&nbsp;Hong-Lei Li,&nbsp;En-Yao Li","doi":"10.1097/FPC.0000000000000498","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000498","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and restrictive behaviors. Mouse nerve growth factor (mNGF), a neurotrophic factor, is critical for neuronal growth and survival, and the mNGF treatment is considered a promising therapy for neurodegeneration. In light of this, we aimed to evaluate the effect of mNGF on neurological function in ASD.</p><p><strong>Methods: </strong>An ASD rat model was established by intraperitoneal injection of valproic acid (VPA). Social behavior, learning, and memory of the rats were measured. TdT-mediated dUTP Nick-end labeling and Nissl assays were performed to detect neuronal apoptosis and survival in the hippocampus and prefrontal cortex. Apoptosis-related proteins and oxidative stress markers were detected.</p><p><strong>Results: </strong>mNGF improved locomotor activity, exploratory behavior, social interaction, and spatial learning and memory in VPA-induced ASD rats. In the hippocampus and prefrontal cortex, mNGF suppressed neuronal apoptosis, increased the number of neurons, superoxide dismutase, and glutathione levels, and decreased reactive oxygen species, nitric oxide, TNF-α, and IL-1β levels compared with the VPA group. In addition, mNGF increased the levels of Bcl-2, p-phosphoinositide-3-kinase (PI3K), and p-serine/threonine kinase (Akt), and decreased the levels of Bax and cleaved caspase-3, while the PI3K inhibitor LY294002 reversed these effects.</p><p><strong>Conclusion: </strong>These data suggest that mNGF suppressed neuronal apoptosis and ameliorated the abnormal behaviors in VPA-induced ASD rats, in part, by activating the PI3K/Akt signaling pathway.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 5","pages":"101-110"},"PeriodicalIF":2.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687520","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":"'Effect of CYP2C19 genetic variants on bleeding and major adverse cardiovascular events in a cohort of Arab patients undergoing percutaneous coronary intervention and stent implantation' by Ali et al. - reassess the evidence, shall we?","authors":"Miriam Saiz-Rodríguez,&nbsp;Pablo Zubiaur,&nbsp;Francisco Abad-Santos","doi":"10.1097/FPC.0000000000000496","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000496","url":null,"abstract":"","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 4","pages":"88-89"},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868943","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":"Associations between four polymorphisms of the SLCO1B1 and effectiveness of the statins: a meta-analysis.","authors":"Hong Ha Nguyen,&nbsp;Cuc Thi Thu Nguyen,&nbsp;Tran Ngoc Phuong Mai,&nbsp;Phung Thanh Huong","doi":"10.1097/FPC.0000000000000490","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000490","url":null,"abstract":"<p><strong>Objective: </strong>Statins are the first-choice therapy for dyslipidemia, but their effectiveness can be influenced by genetic polymorphisms. This study was conducted to assess the association of variants of the solute carrier anion transporter family 1B1 (SLCO1B1) gene, which encodes a transporter involving the hepatic clearance of the statins and their therapeutic efficacy.</p><p><strong>Method: </strong>A systematic review was performed on four electronic databases to identify relevant studies. The pooled mean difference with 95% confidence interval (CI) in percentage change of concentration of LDL-C, total cholesterol (TC), HDL-C, and triglycerides was calculated. Heterogeneity between studies and publication bias, subgroup analyses, and sensitivity analyses were also carried out using R software.</p><p><strong>Results: </strong>Twenty-one studies on 24 365 participants and four variants [rs4149056 (c.521T>C), rs2306283 (c.388A>G), rs11045819 (c.463C>A), rs4363657 (g.89595T>C)] were analyzed. A statistically significant association was found between the LDL-C-lowering effectiveness and the rs4149056 and rs11045819 in the heterozygote model; and the rs4149056, rs2306283, and rs11045819 in the homozygote model. In the subgroup analyses, non-Asian populations, simvastatin, and pravastatin showed significant associations between LDL-C-lowering efficacy and the rs4149056 or rs2306283. Significant associations between the rs2306283 and HDL-C-increasing effectiveness were found in the homozygote model. Regarding TC-reducing, significant associations were observed in the heterozygote and homozygote models of the rs11045819. There was no heterogeneity and publication bias among most studies.</p><p><strong>Conclusion: </strong>SLCO1B1 variants can be used as signals to predict the statins' effectiveness.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 4","pages":"65-78"},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9515903","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}