Frontiers in Genetics最新文献

{"title":"Bibliometric analysis of genomic selection in breeding of animal from 1993 to 2024: global trends and advancements.","authors":"Şenol Çelik","doi":"10.3389/fgene.2024.1402140","DOIUrl":"https://doi.org/10.3389/fgene.2024.1402140","url":null,"abstract":"<p><p>Animal breeding became a difficult science when numerous genes influenced economically significant features. The major source of genetic improvement is selection, and as such, the large generation intervals in these strategies lead to reduced rates of improvement. Therefore, breeding control, genetic improvement research, and selection processes are accelerated by genomic selection. This article regarding global research interest trends in genomic selection in animal breeding themes was examined using bibliometric analysis, which employed papers from 1993 to 2024 from the SCI-Expanded, SSCI, AHCI, and E-SCI indexes. Over the period of 31 years, the first 3,181 published articles on genomic selection in animal breeding were gathered. Additionally, the study displays trends in co-authorships according to nations and academic institutions as well as co-occurrences of author keywords. There have been more articles since 2010 about the use of genomic selection in animal breeding, building up a sizable library of work that will last until 2024. Among the top academics in the field are Calus MPL, Li J, and Wang Y. The most productive institutions were The United Kingdom's University of Edinburgh, Aarhus University (Denmark) and China Agricultural University. The current hotspots in this field of study include \"selection,\" and \"association,\" according to keyword co-occurrence and frequency analysis. China, the United States, Brazil, Canada, and United Kingdom are the top five countries that produced the most papers with the highest levels of international collaboration and networking. The main topics of current study include prediction, accuracy, association, traits, and selection. New techniques for selection, prediction, accuracy, traits, and association were developed as the discipline matured. Research collaborations across countries, institutions, and writers promote knowledge sharing, effective issue resolution, and superior outcomes.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics combined with transcriptomics and physiology reveals the regulatory responses of soybean plants to drought stress.","authors":"Liwei Wang, Peijin He, Mengmeng Hui, Hainan Li, Anni Sun, Hong Yin, Xining Gao","doi":"10.3389/fgene.2024.1458656","DOIUrl":"https://doi.org/10.3389/fgene.2024.1458656","url":null,"abstract":"<p><p>Drought, a prevalent environmental stressor, has had significant consequences on soybean (<i>Glycine max</i> L.), notably impeding its growth and production. Therefore, it is crucial to gain insight into the regulatory responses of soybean plants exposed to drought stress during soybean flowering in the field. In this study, the cultivar 'Liaodou 15' was performed light drought (LD, 24.3% soil moisture content), moderate drought (MD, 20.6% soil moisture content) and severe drought (SD, 16.9% soil moisture content) treatments at flowering stages of soybean and then rehydrated (30% soil moisture content) until harvest. The yield-related indicators were measured and revealed that MD and SD treatments significantly reduced 6.3% and 10.8% of the 100-grain weight. Soybean plants subjected to three drought stresses showed that net photosynthetic rates were 20.8%, 51.5% and 71.8% lower in LD, MD and SD than that of CK. The WUE increased by 31.8%, 31.5% and 18.8% under three drought stress treatments compared to CK. In addition, proline content was 25.94%, 41.01% and 65.43% greater than that of CK under three drought stress treatments. The trend of the MDA content was consistent with that of the proline content. SOD activity was significantly increasing by 10.86%, 46.73% and 14.54% under three drought stress treatments. The activity of CAT in the SD treatment increased by 49.28%. All the indices recovered after rehydration. Furthermore, 54,78 and 51 different expressed metabolomics (DEMs) were identified in the LDCK/LD, MDCK/MD and SDCK/SD groups, respectively. There were 1,211, 1,265 and 1,288 different expressed genes (DEGs) were upregulated and 1,003, 1,819 and 1,747 DEGs were downregulated. Finally, combined transcriptomic and metabolomic analysis suggested that 437 DEGs and 24 DEMs of LDCK/LD group, 741 DEGs and 35 DEMs of MDCK/MD group, 633 DEGs and 23 DEMs of SDCK/SD group, were highly positively correlated in soybean plants under drought stress. Drought stress induced the expression of the <i>PAO1, PAO4, PAO5</i> and <i>P5CS</i> genes to promote the accumulation of spermidine and proline. Our study elucidates the responses of drought-stressed soybean plants in the field and provides a genetic basis for the breeding of drought-tolerant soybean plants.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association and functional genomic analyses for body conformation traits in North American Holstein cattle.","authors":"Luis Paulo B Sousa Junior, Luis Fernando B Pinto, Valdecy A R Cruz, Gerson A Oliveira Junior, Hinayah R Oliveira, Tatiane S Chud, Victor B Pedrosa, Filippo Miglior, Flávio S Schenkel, Luiz F Brito","doi":"10.3389/fgene.2024.1478788","DOIUrl":"https://doi.org/10.3389/fgene.2024.1478788","url":null,"abstract":"<p><p>Body conformation traits are directly associated with longevity, fertility, health, and workability in dairy cows and have been under direct genetic selection for many decades in various countries worldwide. The main objectives of this study were to perform genome-wide association studies and functional enrichment analyses for fourteen body conformation traits using imputed high-density single nucleotide polymorphism (SNP) genotypes. The traits analyzed include body condition score (BCS), body depth (BD), bone quality (BQ), chest width (CW), dairy capacity (DC), foot angle (FAN), front legs view (FLV), heel depth (HDe), height at front end (HFE), locomotion (LOC), rear legs rear view (RLRV), rear legs side view (RLSV), stature (ST), and a composite feet and legs score index (FL) of Holstein cows scored in Canada. De-regressed estimated breeding values from a dataset of 39,135 North American Holstein animals were used as pseudo-phenotypes in the genome-wide association analyses. A mixed linear model was used to estimate the SNP effects, which ranged from 239,533 to 242,747 markers depending on the trait analyzed. Genes and quantitative trait loci (QTL) located up to 100 Kb upstream or downstream of the significant SNPs previously cited in the Animal QTLdb were detected, and functional enrichment analyses were performed for the candidate genes identified for each trait. A total of 20, 60, 13, 17, 27, 8, 7, 19, 4, 10, 13, 15, 7, and 13 genome-wide statistically significant SNPs for Bonferroni correction based on independent chromosomal segments were identified for BCS, BD, BQ, CW, DC, FAN, FLV, HDe, HFE, LOC, RLRV, RLSV, ST, and FL, respectively. The significant SNPs were located across the whole genome, except on chromosomes BTA24, BTA27, and BTA29. Four markers (for BCS, BD, HDe, and RLRV) were statistically significant when considering a much stricter threshold for the Bonferroni correction for multiple tests. Moreover, the genomic regions identified overlap with various QTL previously reported for the trait groups of exterior, health, meat and carcass, milk, production, and reproduction. The functional enrichment analyses revealed 27 significant gene ontology terms. These enriched genomic regions harbor various candidate genes previously reported as linked to bone development, metabolism, as well as infectious and immunological diseases.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Microbial comparative genomics and pangenomics: new tools, approaches and insights into gene and genome evolution.","authors":"Digvijay Verma, Tulasi Satyanarayana, Paulo Jorge Dias","doi":"10.3389/fgene.2024.1490645","DOIUrl":"https://doi.org/10.3389/fgene.2024.1490645","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between gout and kidney stone: results from mendelian randomization and the NHANES study.","authors":"Shengkai Jin, Haochen Geng, Yichen Lu, Yuhua Zhou, Jing Lv, Chaowei Fu, Yuwei Zhang, Menglu Li, Ninghan Feng","doi":"10.3389/fgene.2024.1417663","DOIUrl":"https://doi.org/10.3389/fgene.2024.1417663","url":null,"abstract":"<p><strong>Background: </strong>Kidney stones are a common urologic disease with an increasing incidence year by year, and there are similar influences between gout status and kidney stone incidence. Therefore the contribution of gout status to the incidence of kidney stones is unclear. The aim of this study was to investigate the relationship between gout status and kidney stones and to further explore the causal relationship by Mendelian randomization (MR) analysis.</p><p><strong>Method: </strong>An epidemiologic study of 49,693 participants in the 2009-2018 National Health and Nutrition Examination Survey (NHANES) was conducted to examine the association between the two. The causal relationship between gout status and kidney stones was assessed by Mendelian randomization analysis of data from the GWAS database.</p><p><strong>Result: </strong>A total of 28,742 participants were included in the NHANES analysis. We found that gout status was associated with an increased risk of kidney stones [odds ratio (OR) = 1.45 (95%CI, 1.243-1.692); <i>p</i> < 0.001]. In the MR analysis, we found a causal relationship between gout status and the risk of developing kidney stones (OR = 1.047, 95%CI, 1.011-1.085, <i>p</i> = 0.009).</p><p><strong>Conclusion: </strong>There may be an association between gout status and kidney stone risk. This finding requires further large-sample studies and adequate follow-up.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.","authors":"Suzanne E de Bruijn, Daan M Panneman, Nicole Weisschuh, Elizabeth L Cadena, Erica G M Boonen, Lara K Holtes, Galuh D N Astuti, Frans P M Cremers, Nico Leijsten, Jordi Corominas, Christian Gilissen, Anna Skowronska, Jessica Woodley, Andrew D Beggs, Vasileios Toulis, Di Chen, Michael E Cheetham, Alison J Hardcastle, Terri L McLaren, Tina M Lamey, Jennifer A Thompson, Fred K Chen, John N de Roach, Isabella R Urwin, Lori S Sullivan, Susanne Roosing","doi":"10.3389/fgene.2024.1469686","DOIUrl":"10.3389/fgene.2024.1469686","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods. The aim of this study was to accurately detect novel RP17-SVs by establishing a systematic and efficient workflow.</p><p><strong>Methods: </strong>Genetically unexplained probands diagnosed with adRP (n = 509) from an international cohort were screened using a smMIPs or genomic qPCR-based approach tailored for the RP17 locus. Suspected copy number changes were validated using high-density SNP-array genotyping, and SV breakpoint characterization was performed by mutation-specific breakpoint PCR, genome sequencing and, if required, optical genome mapping. <i>In silico</i> modeling of novel SVs was performed to predict the formation of neo-TADs and whether ectopic contacts between the retinal enhancers and the <i>GDPD1</i>-promoter could be formed.</p><p><strong>Results: </strong>Using this workflow, potential RP17-SVs were detected in eight probands of which seven were confirmed. Two novel SVs were identified that are predicted to cause TAD rearrangement and retinal enhancer-<i>GDPD1</i> contact, one from Germany (DE-SV9) and three with the same SV from the United States (US-SV10). Previously reported RP17-SVs were also identified in three Australian probands, one with UK-SV2 and two with SA-SV3.</p><p><strong>Discussion: </strong>In summary, we describe a validated multi-step pipeline for reliable and efficient RP17-SV discovery and expand the range of disease-associated SVs. Based on these data, RP17-SVs can be considered a frequent cause of adRP which warrants the inclusion of RP17-screening as a standard diagnostic test for this disease.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune regulation and prognostic prediction model establishment and validation of PSMB6 in lung adenocarcinoma.","authors":"Haiyang Zhao, Kexin Luo, Meihan Liu, Yuanze Cai, Siman Liu, Shijuan Li, Yongsheng Zhao, Hongpan Zhang","doi":"10.3389/fgene.2024.1458047","DOIUrl":"10.3389/fgene.2024.1458047","url":null,"abstract":"<p><p>Lung cancer is one of the most common malignant tumors, and patients are often diagnosed at an advanced stage, posing a substantial risk to human health, so it is crucial to establish a model to forecast the prognosis of patients with lung cancer. Recent research has indicated that proteasome 20S subunit 6 (PSMB6) may be closely associated with anti-apoptotic pathways, and proliferation transduction signals in tumor cells of different tumors. However, the precise role of PSMB6 in the immunoregulatory processes within lung adenocarcinoma (LUAD) is yet to be elucidated. By analyzing the TCGA database, we discovered a positive correlation between the expression of PSMB6 and tumor growth trends, and lung adenocarcinoma patients with elevated PSMB6 expression levels had a worse prognosis. Our findings suggest a close correlation between PSMB6 expression levels, immune cell infiltration and immune checkpoint gene expression, which suggests that PSMB6 may become a new independent prognostic indicator. In addition, we developed a prognostic model of PSMB6-regulated immune infiltration-associated genes by analyzing the link between PSMB6 and the immune microenvironment. This model can not only predict the prognosis of lung adenocarcinoma but also forecasts the patient's reaction to immunotherapy. The validity of this research outcome has been confirmed by the GSE31210 and IMvigor210 cohorts. Analysis of the Kaplan-Meier Plotter database indicates that individuals with elevated levels of PSMB6 expression exhibit a poorer prognosis. Additionally, <i>in vitro</i> experiments demonstrated that knockdown of PSMB6 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells while promoting their apoptosis. Overall, our findings suggest that PSMB6 could remarkably influence the management and treatment of lung adenocarcinoma, opening new avenues for targeted immunotherapeutic strategies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Adult patient with <i>WWOX</i> developmental and epileptic encephalopathy: 40 years of observation.","authors":"Anna Teplyshova, Artem Sharkov","doi":"10.3389/fgene.2024.1477466","DOIUrl":"10.3389/fgene.2024.1477466","url":null,"abstract":"<p><p>WWOX developmental and epileptic encephalopathy is characterised by drug-resistant epilepsy with onset within the first year of life and severe psychomotor developmental delay. This report presents for the first time a clinical case of an adult patient with a homozygous likely pathogenic variant (p.Thr12Met) in the <i>WWOX</i> gene, with more than 40 years of follow-up. The patient had refractory epilepsy with various types of seizures during his life: mainly epileptic spasms, autonomic, myoclonic, tonic seizures, and absences. The patient had a prominent developmental delay with a lack of expressive speech, but by the age of 3, he had acquired the skills to sit, crawl, and walk with support. In adolescence, there was an acute regression of acquired skills to a total absence of independent motor activity. The patient had dysmorphic features, such as upslanting palpebral fissures, arched eyebrows, and hypertelorism. For many years, the patient was given a diagnosis of cerebral palsy; 38 years after the onset of the disease, he was given a molecular genetic diagnosis of <i>WWOX</i>-associated developmental and epileptic encephalopathy. Our observation illustrates the natural history of <i>WWOX</i>-DEE and the high clinical significance of early genetic diagnostics for identifying the cause of developmental delay and resistant epilepsy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroplast genome sequencing and divergence analysis of 18 <i>Pyrus</i> species: insights into intron length polymorphisms and evolutionary processes.","authors":"Jung Sun Kim, Hoyong Chung, Bohyeon Park, Karpagam Veerappan, Yoon-Kyung Kim","doi":"10.3389/fgene.2024.1468596","DOIUrl":"10.3389/fgene.2024.1468596","url":null,"abstract":"<p><p>Pears constitute an essential temperate crop and are primarily produced through interspecific hybridization owing to self-incompatibility that complicates their breeding history. To address this, we sequenced the complete chloroplast (cp) genomes of 18 <i>Pyrus</i> and one <i>Malu</i>s species using the Illumina HiSeq4000 platform. The cp genomes ranged from 159,885 bp to 160,153 bp and exhibited a conserved circular DNA structure with an average GC content of 36.5%. Each cp genome contained 127 genes, including 83 protein-coding, 36 tRNA, and 8 rRNA genes. Divergence analysis with mVISTA showed high conservation in the coding regions and notable variations in the non-coding regions. All species shared 17 intron-containing genes, with <i>ycf3</i> and <i>clpP</i> each having two introns. Five intron-containing genes (<i>ndhB</i>, <i>rpl2</i>, <i>rps12</i>, <i>trnA-UGC</i>, and <i>trnE-UUC</i>) were located in the inverted repeat regions, while <i>trnL-UAA</i> was located in the large single-copy region, with conserved intron lengths across Pomoideae. We identified polymorphic intron sequences in the <i>rpl22</i>, <i>petB</i>, <i>clpP</i>, <i>ndhA</i>, and <i>rps16</i> genes and designed primers for these regions. Notably, the two <i>Pyrus ussuriensis</i> accessions Doonggeullebae and Cheongdangrori showed intron-length polymorphisms despite being classified as the same species. Phylogenetic analysis of the cp genome sequences revealed two major clusters, indicating distinct maternal lineages and evolutionary origins. This study underscores the importance of cp gene polymorphisms in <i>P. fauriei</i>, <i>P. calleryana</i>, <i>P. ussuriensis</i>, and <i>P. pyrifolia</i>, providing valuable insights into <i>Pyrus</i> evolution as well as aiding in the conservation and breeding of pear germplasm.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of <i>NR1I3</i> and <i>NR1H4</i> polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study.","authors":"Xiaoyan Xu, Ruina Chen, Lihuan Lu, Jingru Cheng, Xiaomin He, Hongqiu Pan, Meiling Zhang, Honggang Yi, Shaowen Tang","doi":"10.3389/fgene.2024.1428319","DOIUrl":"https://doi.org/10.3389/fgene.2024.1428319","url":null,"abstract":"<p><strong>Objective: </strong>The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (<i>NR1I3</i>) and nuclear receptor subfamily 1 Group H member 4 (<i>NR1H4</i>) genes to the risk of AT-DILI in the Chinese population.</p><p><strong>Methods: </strong>A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the <i>NR1I3</i> and <i>NR1H4</i> genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes.</p><p><strong>Results: </strong>224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of <i>NR1H4</i> rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, <i>p</i> = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, <i>p</i> = 0.008; 15.5 μmol/L vs. 15.0 μmol/L vs. 13.7 μmol/L, <i>p</i> = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of <i>NR1H4</i> rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, <i>p</i> = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, <i>p</i> = 0.019, respectively).</p><p><strong>Conclusion: </strong>Based on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the <i>NR1H4</i> gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}