Pharmacogenetics and genomics最新文献

{"title":"CFTR genotype-phenotype associations and clinical outcomes in pediatric cystic fibrosis.","authors":"Luana da Silva Baptista Arpini, Fernanda Mayrink Gonçalves Liberato, Sabrina da Silva Santos, Gina Torres Rego Monteiro","doi":"10.1097/FPC.0000000000000601","DOIUrl":"10.1097/FPC.0000000000000601","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between CFTR genotypes and clinical and nutritional outcomes in children and adolescents with cystic fibrosis (CF) receiving care within the public health system of Espírito Santo, Brazil.</p><p><strong>Methods: </strong>This cross-sectional study retrospectively analyzed clinical and genetic data from 110 individuals under 18 years with confirmed CF, followed at a state reference center between 2007 and 2024. CFTR variants were classified by functional consequence and grouped by severity. Outcomes included pancreatic insufficiency, forced expiratory volume in 1 s (FEV1%), Shwachman-Kulczycki score, nutritional status, and chronic airway colonization by Pseudomonas aeruginosa . Associations were assessed using appropriate statistical tests.</p><p><strong>Results: </strong>A high degree of CFTR genotypic heterogeneity was observed, with predominance of the F508del variant (72.7%) alongside a substantial proportion of non-F508del and rare pathogenic variants. Individuals carrying two class I-III variants had a higher frequency of pancreatic insufficiency ( P = 0.026). The presence of p.Phe508del was associated with worse pulmonary function ( P = 0.031) and bone demineralization ( P = 0.026). The Shwachman-Kulczycki score correlated negatively with age and age at diagnosis and positively with BMI z -score and FEV1%. No significant associations were found between genotype and chronic P. aeruginosa colonization, liver disease, or overall disease severity.</p><p><strong>Conclusion: </strong>CFTR genotypic heterogeneity was high, with minimal function variants associated with poorer clinical outcomes. The notable presence of rare variants underscores the need for regional studies to better characterize phenotypic variability and support precision medicine strategies in middle-income settings.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"163-170"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777831","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":"TWSG1 variation identifies a ustekinumab-response phenotype in patients with inflammatory bowel disease.","authors":"Mohammed Alkhalifa, Gio R Dela Cruz, Terry Ponich, James C Gregor, Brian Yan, Reena Khanna, Keith McIntosh, Melanie D Beaton, Richard B Kim, Aze Wilson","doi":"10.1097/FPC.0000000000000602","DOIUrl":"10.1097/FPC.0000000000000602","url":null,"abstract":"<p><strong>Objectives: </strong>A genome-wide association study identified that genetic variation in the twisted gastrulation protein homolog-1 gene ( TWSG1 rs7242593) was linked to early clinical remission in ustekinumab-exposed patients in the UNITI clinical trials. We aimed to confirm if a single nucleotide variation (SNV) in the TWSG1 gene is associated with clinical remission in inflammatory bowel disease (IBD) patients on ustekinumab.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted in ustekinumab-treated IBD patients. Participants underwent screening for the TWSG1 SNV rs7242593 and were assessed for clinical disease remission by Harvey-Bradshaw Index or partial Mayo score at 3 and 12 months. Ustekinumab dose and treatment duration were also assessed.</p><p><strong>Results: </strong>A total of 125 IBD participants were included (wild-type genotype, CC, n  = 108; variant genotype, CT, n  = 17). Participants in the variant genotype group were more likely to achieve clinical remission at 3 months [odds ratio (OR): 23.11, 95% confidence interval (CI) = 3.92-449.40, adjusted P  = 0.0043] and at 12 months (OR = 17.75, 95%CI = 2.42-381.0, adjusted P  = 0.016) on standard ustekinumab dosing and less likely to discontinue therapy during the follow-up period (hazard ratio=4.20, 95% CI = 1.94-9.09, P  = 0.02). For wild-type carriers, ustekinumab dose escalations were not associated with disease remission at any time.</p><p><strong>Conclusion: </strong>TWSG1 SNV was associated with early and persistent clinical remission in ustekinumab-exposed IBD patients. Wild-type carriers who did not achieve remission were not rescued with high-dose treatment.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"157-162"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729646","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":"Characteristics of initial pharmacogenetic testing and subsequent physician referral behavior in youth mental health.","authors":"Naomi Lemboye, Madison Heintz, Abdullah Al Maruf, Sarker M Shaheen, Ryden McCloud, Laina McAusland, Paul D Arnold, Chad A Bousman","doi":"10.1097/FPC.0000000000000603","DOIUrl":"10.1097/FPC.0000000000000603","url":null,"abstract":"<p><p>While prior studies have focused on the clinical utility of pharmacogenetic (PGx) testing, less is known about factors that influence physicians' continued use of PGx testing in routine practice. Using data from the PGx-SParK trial, we examined whether the actionability of PGx test results from a physician's initial referral predicted subsequent PGx referral behavior. Youth aged 6-24 years referred for PGx testing in Western Canada between October 2020 and November 2025 were included. For each physician, an index PGx referral was identified and linked to patient characteristics, testing turnaround time, and CYP2B6, CYP2C19, and CYP2D6 results. Actionability for psychotropic prescribing was defined based on current PGx guidelines and categorized as current, future, or none. The number of subsequent referrals per physician was modeled using generalized linear models with a Poisson distribution corrected for overdispersion and adjusted for follow-up time and relevant covariates. Among 371 physician index referrals, 90% of tested youth had at least one current (22%) or future (68%) actionable result. Over a mean follow-up of 29 months, 52% of physicians made at least one subsequent PGx referral. Neither current nor future actionability of the initial PGx test results was associated with subsequent referral behavior. However, patient age (older) and physician speciality (psychiatrists) were associated with greater odds of a subsequent referral. These findings suggest that sustained physician engagement with PGx testing in youth mental healthcare may be driven more by implementation context and physician-level factors than by the clinical actionability of test results.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"171-175"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729654","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":"Prevalence of TPMT and NUDT15 diplotypes in Mexican children with B-cell acute lymphoblastic leukemia.","authors":"Joaquin Garcia-Solorio, Carolina Molina-Garay, Víctor Jesús Sánchez-Martínez, Beatriz Eugenia Villegas-Torres, Irlanda Campos-Perez, Marco Jiménez-Olivares, Fernanda Flores-Espino, Diana Casique-Aguirre, Juan Carlos Núñez-Enriquez, Janet Flores-Lujano, Minerva Mata-Rocha, José Gabriel Peñaloza-Gonzalez, Victor Hugo Olivares-Villalpando, Ma Del Rocío Baños-Lara, Ángel García-Soto, César Alejandro Galván-Díaz, Alberto Olaya-Vargas, Moises Solano-Cardozo, Miguel Ángel Garrido-Hernández, Nuria Citlalli Luna-Silva, Lena Sarahi Cano-Cuapio, Karol Carrillo-Sanchez, Luis Leonardo Flores-Lagunes, Elvia Cristina Mendoza-Caamal, Vincent González-Osnaya, Rosana Pelayo-Camacho, Juan Manuel Mejía-Arangure, Jun J Yang, Carmen Alaez-Verson","doi":"10.1097/FPC.0000000000000593","DOIUrl":"10.1097/FPC.0000000000000593","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the allelic and diplotype variability of TPMT and NUDT15 in pediatric patients with B-cell acute lymphoblastic leukemia from the central-southern region of Mexico.</p><p><strong>Methods: </strong>Samples from 275 pediatric B-cell acute lymphoblastic leukemia patients were analyzed. Next-generation sequencing was used for TPMT and NUDT15 genotyping. Alleles and diplotypes were assessed according to the Clinical Pharmacogenetics Implementation Consortium guidelines. Their geographic distribution was compared across Mexican states and global populations. In-silico analyses were conducted to assess the structural and functional impact of TPMT variants not associated with star alleles.</p><p><strong>Results: </strong>The wild-type *1 allele, associated with normal enzymatic activity, was predominant in both genes: TPMT (94.15%) and NUDT15 (90.45%). TPMT showed greater allelic diversity compared with previous studies in Mexican populations. Alleles conferring absent or indeterminate enzymatic activity in TPMT were distributed across six diplotypes (11.62%), with *3A allele (4.73%) and *1 / *3A diplotype (9.45%) being the most frequent. Additionally, two unclassified TPMT variants, p.G126A and p.D137Y, were identified. For NUDT15 , three non-wild-type diplotypes were observed (19.09%), with the *2 allele (6.74%) and *1* / 2 diplotype (13.48%) being the most prevalent.</p><p><strong>Conclusion: </strong>Approximately 28% of patients carried TPMT and/or NUDT15 variants associated with non-wild-type enzymatic activity, increasing the risk of mercaptopurine-induced myelotoxicity. Preemptive genotyping is essential to reduce toxicity, optimize treatment, and advance precision medicine in this population. Additionally, the two TPMT variants p.G126A and p.D137Y, currently not classified within Clinical Pharmacogenetics Implementation Consortium-defined star alleles, highlight the need for functional validation and potential clinical classification to improve pharmacogenetic interpretation in diverse populations.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"143-150"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106679","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":"Application of risk priority number of failure mode and effects analysis to drug-variant pairs for severe cutaneous adverse reactions in Korean and American populations.","authors":"Hyun Kyung Lee, Min Ju Kang, Hajung Kim, Ha Young Jang, Nayoung Han, In-Wha Kim, Jung Mi Oh","doi":"10.1097/FPC.0000000000000596","DOIUrl":"10.1097/FPC.0000000000000596","url":null,"abstract":"<p><strong>Objectives: </strong>Given the varying frequency and significance of genetic factors associated with severe cutaneous adverse reactions (SCARs) across different ethnicities, this study aimed to identify high-risk priority drug-variant pairs by considering genetic differences between Korea and the USA to inform preventive strategies.</p><p><strong>Methods: </strong>A list of drug-variant pairs associated with SCARs was identified using the Pharmacogenomics Knowledge Base. Prioritization of drug-variant pairs for preventive strategies was conducted using the risk priority number (RPN) method incorporating expert opinions in the field of drug allergy. The RPN for each drug-variant was calculated based on severity, probability, and detectability, with each parameter derived as an odds ratio of the genetic variant associated with SCARs, the occurrence frequency of drug-associated SCARs, and the variant prevalence in Korean and American populations, respectively. Higher values were evaluated as higher priority.</p><p><strong>Results: </strong>A total of 80 drug-variant pairs from 16 drugs associated with SCARs were identified in Koreans, and 12 drug-variant pairs from four drugs in Americans. Six drug-variant pairs were included in Korean drug labels, while only two drug-variant pairs were included in US drug labels. In Koreans, the highest priority drug-variant pair was rs3131003 for allopurinol, which is in moderate linkage disequilibrium with HLA-B*58:01 , whereas in Americans, HLA-B*58:01 itself for allopurinol was the highest priority variant.</p><p><strong>Conclusion: </strong>Drug-variant pairs with high RPN scores can be prioritized in clinical strategies to prevent SCARs in Korean and American populations. Incorporating these findings into clinical practices could ultimately contribute to the safe use of drugs.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"125-133"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474924","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":"Effects of apolipoprotein E and solute carrier organic anion transporter family member 1B1 gene polymorphisms on statin efficacy and safety in dyslipidemic patients.","authors":"Xiaohong Wu, Yumei Cai, Yonglong Su, Xianni Wei, Tingting Nan, Xiaoyun Ye, Siheng Lian, Jinbao Wei","doi":"10.1097/FPC.0000000000000598","DOIUrl":"10.1097/FPC.0000000000000598","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the distribution of the apolipoprotein E ( ApoE ) and solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) polymorphisms in dyslipidemia patients and their impact on statin efficacy and safety.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on dyslipidemic inpatients (April 2024-March 2025) who received statin therapy and genetic testing for SLCO1B1 (rs4149056) and ApoE (rs429358 and rs7412), to analyze the association of genotypes with lipid levels and safety indicators.</p><p><strong>Results: </strong>The final analysis included 238 hospitalized patients with dyslipidemia (156 males and 82 females) who met the inclusion criteria. The study population had a mean age of 60.61 ± 0.91 years (mean ± SEM). The allele frequencies for both ApoE and SLCO1B1 polymorphisms were in Hardy-Weinberg equilibrium ( P  > 0.05). Analysis of statin efficacy revealed a significant association between ApoE genotype and atorvastatin response: E3 carriers demonstrated higher low-density lipoprotein cholesterol levels posttreatment compared to E2 carriers (2.85 ± 1.00 mmol/l vs. 2.28 ± 0.96 mmol/l, P  = 0.026). However, no such association was found in patients administered rosuvastatin. For safety outcomes, comparisons of creatine kinase and alanine aminotransferase levels between carriers of the SLCO1B1 TC and TT genotypes showed no statistically significant differences.</p><p><strong>Conclusion: </strong>APOE polymorphisms influence statin efficacy. The E2 genotype is associated with better atorvastatin efficacy in lipid management. At low-to-moderate doses, the SLCO1B1 TC genotype did not increase safety risk, supporting its clinical safety.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"151-156"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491498","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":"The potential effect and pathway of valsartan: genome-wide and phenome-wide association study from UK Biobank data.","authors":"Shengyin Zeng, Yaxin Li, Yucong Zhang, Yueqi Lu, Lei Ruan, Cuntai Zhang, Jianguo Zhang, Bangwei Chen, Tao Li","doi":"10.1097/FPC.0000000000000597","DOIUrl":"10.1097/FPC.0000000000000597","url":null,"abstract":"<p><strong>Purpose: </strong>Valsartan, an angiotensin II receptor blocker, is widely used for hypertension and heart failure. While its cardiovascular benefits are established, its broader pharmacological effects remain incompletely characterized. This study aimed to identify genetic variants associated with valsartan use and to systematically explore its potential effects and adverse events across a wide range of phenotypes.</p><p><strong>Methods: </strong>Using UK Biobank data, we selected participants of European ancestry prescribed valsartan as cases, compared with controls not prescribed any ARBs. A genome-wide association study (GWAS) was conducted to identify suggestive genetic variants associated with valsartan use. These variants were then used as instruments in a phenome-wide association study (PheWAS) to screen for associated traits. Mendelian randomization analyses, including inverse-variance weighted and pleiotropy-robust methods, were employed to assess potential causal relationships.</p><p><strong>Results: </strong>The GWAS identified 19 suggestive single nucleotide polymorphisms ( P  < 1 × 10 -5 ) near genes, including PREP , GCLC , and ZNF133 . The PheWAS analysis revealed associations with 14 phenotypes, including lower levels of total cholesterol ( β = -0.59) and low-density lipoprotein cholesterol (LDL-C) ( β = -0.56), and increased risk of cough (odds ratio = 1.67). Mendelian randomization provided genetic evidence consistent with potential causal effects of valsartan in lowering LDL-C ( β = -2.34 × 10 -3 ) and reducing the risk of transient cerebral ischemic attack.</p><p><strong>Conclusion: </strong>Our genetic-based study suggests valsartan use may be associated with lowered LDL-C and reduced risks of certain ischemic cardiovascular events. These findings generate novel hypotheses regarding the drug's pleiotropic effects and potential applications beyond hypertension management, which warrant further clinical investigation.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"134-142"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491500","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":"Impact of genetic polymorphisms on the sulfation of dehydroepiandrosterone and 17-β estradiol by human cytosolic sulfotransferase SULT2B1a.","authors":"Eid Alatwi, Ahsan F Bairam","doi":"10.1097/FPC.0000000000000561","DOIUrl":"10.1097/FPC.0000000000000561","url":null,"abstract":"<p><strong>Background: </strong>Dehydroepiandrosterone (DHEA) is considered an endogenous steroid hormone precursor, and 17-ß estradiol (E2) is one of the estrogen steroid hormones. Of the 13 known human cytosolic sulfotransferases (SULTs), SULT2B1a has been shown to be expressed in steroid hormone-responsive tissues such as the prostate, ovary, and placenta, as well as the fetal brain. Previous studies have demonstrated that SULT2B1a is capable of sulfating 3β-hydroxysteroids such as DHEA and pregnenolone. The present study aimed to investigate the effects of human SULT2B1 single-nucleotide polymorphisms (SNPs) on the enzymatic characteristics of SULT2B1a allozymes in mediating the sulfation of DHEA and E2.</p><p><strong>Methods: </strong>To inspect the effects of SNPs of the SULT2B1 gene on the sulfation of DHEA and E2 by SULT2B1a allozymes, 13 recombinant SULT2B1a allozymes were produced, expressed, and purified using established procedures. Thirteen SULT 2B1a nonsynonymous missense coding SNPs (cSNPs) were selected among numerous identified human SULT 2B1a SNPs by a comprehensive database search. The corresponding cDNAs, packaged in pGEX-2TK expression vector, and encoding the selected 13 SULT2B1a allozymes, have been generated by performing site-directed mutagenesis. These were then bacterially expressed in BL21 E. coli cells and purified using glutathione-Sepharose affinity chromatography. The purified allozymes were tested for their ability to sulfonate DHEA and E2.</p><p><strong>Results: </strong>In terms of the kinetic parameters, the wild-type SULT2B1a exhibited higher enzyme affinity toward DHEA than with E2. In comparison with the wild-type SULT2B1a, the purified allozymes displayed differential sulfating activities toward DHEA and E2.</p><p><strong>Conclusion: </strong>Accordingly, these findings indicate an apparent effect of SULT2B1 cSNPs on the sulfating activities of SULT2B1a allozymes toward DHEA and E2, and may provide for a better understanding of the pharmacokinetics of DHEA and E2 in individuals with differing SULT2B1a genotypes.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"48-55"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12846738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452691","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":"Leveraging implementation science to enhance the adoption of DPYD testing.","authors":"Sony Tuteja, J Kevin Hicks, Larisa H Cavallari, Nihal El Rouby, D Max Smith, Jai N Patel, Daniel L Hertz","doi":"10.1097/FPC.0000000000000581","DOIUrl":"10.1097/FPC.0000000000000581","url":null,"abstract":"","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"80-82"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757163","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":"No interaction between genetic variants and DNA methylation of the ferrochelatase gene in relation to antituberculosis drug-induced liver injury.","authors":"Fei Wang, Meiling Zhang, Yu Wu, Jingru Cheng, Ruina Chen, Hongqiu Pan, Lihuan Lu, Xiaomin He, Honggang Yi, Shaowen Tang","doi":"10.1097/FPC.0000000000000583","DOIUrl":"10.1097/FPC.0000000000000583","url":null,"abstract":"<p><strong>Objective: </strong>The pathogenic mechanisms of antituberculosis drug-induced liver injury (AT-DILI) remain unclear. Isoniazid and rifampicin may lead to hepatic accumulation of protoporphyrin IX in which heme synthesis ferrochelatase (FECH), a key rate-limiting enzyme, potentially plays an important role. This study aimed to investigate the combined effects of FECH gene polymorphisms and promoter methylation on AT-DILI risk in the Eastern Chinese population.</p><p><strong>Methods: </strong>A 1 : 1 matched case-control study was conducted, detecting one CpG island in the FECH promoter and four single-nucleotide polymorphisms (SNPs). A multivariate conditional logistic regression was used to estimate the association between genotypes and the risk of AT-DILI by the odds ratios (OR) with 95% confidence intervals (CIs). Additive and multiplicative interactions between methylation status and SNPs were further analyzed: additive interactions via the relative excess risk due to interaction (RERI) with 95% CIs, and multiplicative interactions by incorporating methylation-SNP product terms into regression models.</p><p><strong>Results: </strong>Overall, 182 cases and 182 controls were included. Neither FECH promoter methylation (adjusted OR: 0.978, 95% CI: 0.408-1.560, P  = 0.509) nor the four SNPs showed individual associations with AT-DILI risk ( P  > 0.05). Crossover analyses revealed no significant genotype-methylation interactions ( P  > 0.05). Both additive (rs17063905 RERI: -0.556, P  = 0.691) and multiplicative interaction models (rs17063905, OR: 0.723, P  = 0.615) demonstrated no synergistic effects between methylation and polymorphisms.</p><p><strong>Conclusion: </strong>This research finds no significant association between FECH promoter methylation status in the CpG island, polymorphisms, or their interactions and the risk of AT-DILI.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"71-79"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534476","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}