Awol Mekonnen Ali, Haileyesus Adam, Daniel Hailu, Rawleigh Howe, Teferra Abula, Marieke J H Coenen
{"title":"评估埃塞俄比亚亚的斯亚贝巴儿童急性淋巴细胞白血病中CNOT3、GRIA1、NFATC2和PNPLA3变异等位基因的频率及其与l -天冬酰胺酶过敏的关系","authors":"Awol Mekonnen Ali, Haileyesus Adam, Daniel Hailu, Rawleigh Howe, Teferra Abula, Marieke J H Coenen","doi":"10.2147/TACG.S404695","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>L-asparaginase is a vital component for the treatment of childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions and hepatotoxicity hinder its anti-neoplastic efficacy. Previous reports indicated that genetic variants in <i>CNOT3, GRIA1</i>, and <i>NFATC2</i> genes might be associated with hypersensitivity reactions and <i>PNPLA3</i> with liver function.</p><p><strong>Objective: </strong>In this study, it was investigated whether this association also exists in a pediatric ALL cohort from Ethiopia.</p><p><strong>Methods: </strong>Three variants <i>GRIA1</i> rs4958351, <i>CNOT3</i> rs73062673, and <i>NFATC2</i> rs6021191 were genotyped in a cohort of 160 patients. Association analysis to investigate the association with hypersensitivity reactions was performed using logistic regression analyses. Besides these variants, a variant in <i>PNPLA3</i> (rs738409) was genotyped to assess the association with liver function.</p><p><strong>Results: </strong>Genotype frequencies of <i>GRIA1</i> rs4958351, <i>CNOT3</i> rs73062673, and <i>NFATC2</i> rs6021191 were higher/lower than previously reported. One hundred and forty-four patients were included in the association analysis of which, 18 (12.5%) developed L-ASP hypersensitivity. Though the frequency of hypersensitivity was higher in patients that carried the risk alleles of the three investigated genes, no statistically significant differences were observed. Association analysis between <i>PNPLA3</i> rs738409 and liver function could not be investigated due to a lack of clinical information.</p><p><strong>Conclusion: </strong>In conclusion, none of the tested genes did predict L-asparaginase hypersensitivity in an Ethiopian pediatric ALL patients.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/a9/tacg-16-131.PMC10404408.pdf","citationCount":"0","resultStr":"{\"title\":\"Evaluating the Frequencies of <i>CNOT3, GRIA1, NFATC2</i>, and <i>PNPLA3</i> Variant Alleles and Their Association with L-Asparaginase Hypersensitivity in Pediatric Acute Lymphoblastic Leukemia in Addis Ababa, Ethiopia.\",\"authors\":\"Awol Mekonnen Ali, Haileyesus Adam, Daniel Hailu, Rawleigh Howe, Teferra Abula, Marieke J H Coenen\",\"doi\":\"10.2147/TACG.S404695\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>L-asparaginase is a vital component for the treatment of childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions and hepatotoxicity hinder its anti-neoplastic efficacy. Previous reports indicated that genetic variants in <i>CNOT3, GRIA1</i>, and <i>NFATC2</i> genes might be associated with hypersensitivity reactions and <i>PNPLA3</i> with liver function.</p><p><strong>Objective: </strong>In this study, it was investigated whether this association also exists in a pediatric ALL cohort from Ethiopia.</p><p><strong>Methods: </strong>Three variants <i>GRIA1</i> rs4958351, <i>CNOT3</i> rs73062673, and <i>NFATC2</i> rs6021191 were genotyped in a cohort of 160 patients. Association analysis to investigate the association with hypersensitivity reactions was performed using logistic regression analyses. Besides these variants, a variant in <i>PNPLA3</i> (rs738409) was genotyped to assess the association with liver function.</p><p><strong>Results: </strong>Genotype frequencies of <i>GRIA1</i> rs4958351, <i>CNOT3</i> rs73062673, and <i>NFATC2</i> rs6021191 were higher/lower than previously reported. One hundred and forty-four patients were included in the association analysis of which, 18 (12.5%) developed L-ASP hypersensitivity. Though the frequency of hypersensitivity was higher in patients that carried the risk alleles of the three investigated genes, no statistically significant differences were observed. Association analysis between <i>PNPLA3</i> rs738409 and liver function could not be investigated due to a lack of clinical information.</p><p><strong>Conclusion: </strong>In conclusion, none of the tested genes did predict L-asparaginase hypersensitivity in an Ethiopian pediatric ALL patients.</p>\",\"PeriodicalId\":39131,\"journal\":{\"name\":\"Application of Clinical Genetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/a9/tacg-16-131.PMC10404408.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Application of Clinical Genetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/TACG.S404695\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Application of Clinical Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/TACG.S404695","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
l -天冬酰胺酶是治疗儿童急性淋巴细胞白血病(ALL)的重要成分;然而,超敏反应和肝毒性阻碍了其抗肿瘤作用。先前的报道表明,CNOT3、GRIA1和NFATC2基因的遗传变异可能与超敏反应有关,PNPLA3与肝功能有关。目的:在本研究中,研究了这种关联是否也存在于来自埃塞俄比亚的儿科ALL队列中。方法:对160例患者的3种变异GRIA1 rs4958351、CNOT3 rs73062673和NFATC2 rs6021191进行基因分型。采用logistic回归分析进行关联分析,以调查与超敏反应的关系。除了这些变异外,PNPLA3的一个变异(rs738409)被基因分型以评估其与肝功能的关系。结果:GRIA1 rs4958351、CNOT3 rs73062673、NFATC2 rs6021191基因型频率均高于/低于文献报道。144例患者纳入关联分析,其中18例(12.5%)发生L-ASP超敏反应。虽然携带上述三种基因风险等位基因的患者出现超敏反应的频率较高,但差异无统计学意义。由于缺乏临床资料,无法对PNPLA3 rs738409与肝功能的相关性进行分析。结论:总而言之,所有检测的基因都不能预测埃塞俄比亚儿科ALL患者的l -天冬酰胺酶过敏。
Evaluating the Frequencies of CNOT3, GRIA1, NFATC2, and PNPLA3 Variant Alleles and Their Association with L-Asparaginase Hypersensitivity in Pediatric Acute Lymphoblastic Leukemia in Addis Ababa, Ethiopia.
Introduction: L-asparaginase is a vital component for the treatment of childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions and hepatotoxicity hinder its anti-neoplastic efficacy. Previous reports indicated that genetic variants in CNOT3, GRIA1, and NFATC2 genes might be associated with hypersensitivity reactions and PNPLA3 with liver function.
Objective: In this study, it was investigated whether this association also exists in a pediatric ALL cohort from Ethiopia.
Methods: Three variants GRIA1 rs4958351, CNOT3 rs73062673, and NFATC2 rs6021191 were genotyped in a cohort of 160 patients. Association analysis to investigate the association with hypersensitivity reactions was performed using logistic regression analyses. Besides these variants, a variant in PNPLA3 (rs738409) was genotyped to assess the association with liver function.
Results: Genotype frequencies of GRIA1 rs4958351, CNOT3 rs73062673, and NFATC2 rs6021191 were higher/lower than previously reported. One hundred and forty-four patients were included in the association analysis of which, 18 (12.5%) developed L-ASP hypersensitivity. Though the frequency of hypersensitivity was higher in patients that carried the risk alleles of the three investigated genes, no statistically significant differences were observed. Association analysis between PNPLA3 rs738409 and liver function could not be investigated due to a lack of clinical information.
Conclusion: In conclusion, none of the tested genes did predict L-asparaginase hypersensitivity in an Ethiopian pediatric ALL patients.