S Ioannou, A Beecham, L Gomez, R Dauer, N Khakoo, L Pascual, M Quintero, J Lopez, J S Leavitt, N Solis, M Ortega, A R Deshpande, D H Kerman, S Proksell, E A Torres, T Haritunians, D Li, M T Abreu, D P B McGovern, J L McCauley, O M Damas
{"title":"药物基因组学中的祖先多样性会影响西班牙裔/拉丁裔炎症性肠病患者的治疗。","authors":"S Ioannou, A Beecham, L Gomez, R Dauer, N Khakoo, L Pascual, M Quintero, J Lopez, J S Leavitt, N Solis, M Ortega, A R Deshpande, D H Kerman, S Proksell, E A Torres, T Haritunians, D Li, M T Abreu, D P B McGovern, J L McCauley, O M Damas","doi":"10.1016/j.cgh.2024.07.032","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and aims: </strong>The prevalence of inflammatory bowel disease (IBD) among Hispanic/Latine communities is increasing. Pharmacogenomic studies reveal genetic markers that influence treatment decisions. The aim of our study was to examine the frequency and impact of genetic polymorphisms on thiopurine-associated leukopenia (NUDT15, TPMT) and anti-TNF immunogenicity (HLA-DQA1*05) in a cohort of Hispanic patients of diverse ancestral backgrounds.</p><p><strong>Methods: </strong>We performed a multicenter, retrospective cohort study comprised of 2225 Hispanic participants. We measured the frequency of variation affecting drug response in NUDT15, TPMT, and HLA-DQA1*05, their ancestral origin (European, African, or Amerindian), and the rate of development of myelosuppression and immunogenicity to thiopurines and anti-TNFs, respectively, in exposed patients.</p><p><strong>Results: </strong>NUDT15 and TPMT variants were rare, except for rs116855232 in NUDT15 which was common only in alleles of Amerindian origin. All NUDT15 variant alleles were inherited on an Amerindian haplotype, and among the Amerindian allele subset, the variant frequency of NUDT15*4 (rs147390019) was a remarkable 23% in patients with leukopenia but only 3% in patients without leukopenia. HLA-DQA1*05 and its European tagging variant rs2097432 were common in alleles from all ancestral origins and demonstrated association with immunogenicity to anti-TNFs. However, rs2097432 was only correlated with HLA-DQA1*05 in the European allele subset.</p><p><strong>Conclusion: </strong>These findings indicate that NUDT15 testing should become standard clinical practice before prescribing thiopurines in individuals with Amerindian ancestry, including Hispanic individuals. Additionally, rs2097432 should not be used as a surrogate for HLA-DQA1*05 testing for diverse populations. Ultimately, incorporating ancestry in personalized therapeutic approaches is important for treatment of Hispanic patients with IBD.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":11.6000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ancestral diversity in pharmacogenomics affects treatment for Hispanic/Latine populations with inflammatory bowel disease.\",\"authors\":\"S Ioannou, A Beecham, L Gomez, R Dauer, N Khakoo, L Pascual, M Quintero, J Lopez, J S Leavitt, N Solis, M Ortega, A R Deshpande, D H Kerman, S Proksell, E A Torres, T Haritunians, D Li, M T Abreu, D P B McGovern, J L McCauley, O M Damas\",\"doi\":\"10.1016/j.cgh.2024.07.032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and aims: </strong>The prevalence of inflammatory bowel disease (IBD) among Hispanic/Latine communities is increasing. Pharmacogenomic studies reveal genetic markers that influence treatment decisions. The aim of our study was to examine the frequency and impact of genetic polymorphisms on thiopurine-associated leukopenia (NUDT15, TPMT) and anti-TNF immunogenicity (HLA-DQA1*05) in a cohort of Hispanic patients of diverse ancestral backgrounds.</p><p><strong>Methods: </strong>We performed a multicenter, retrospective cohort study comprised of 2225 Hispanic participants. We measured the frequency of variation affecting drug response in NUDT15, TPMT, and HLA-DQA1*05, their ancestral origin (European, African, or Amerindian), and the rate of development of myelosuppression and immunogenicity to thiopurines and anti-TNFs, respectively, in exposed patients.</p><p><strong>Results: </strong>NUDT15 and TPMT variants were rare, except for rs116855232 in NUDT15 which was common only in alleles of Amerindian origin. All NUDT15 variant alleles were inherited on an Amerindian haplotype, and among the Amerindian allele subset, the variant frequency of NUDT15*4 (rs147390019) was a remarkable 23% in patients with leukopenia but only 3% in patients without leukopenia. HLA-DQA1*05 and its European tagging variant rs2097432 were common in alleles from all ancestral origins and demonstrated association with immunogenicity to anti-TNFs. However, rs2097432 was only correlated with HLA-DQA1*05 in the European allele subset.</p><p><strong>Conclusion: </strong>These findings indicate that NUDT15 testing should become standard clinical practice before prescribing thiopurines in individuals with Amerindian ancestry, including Hispanic individuals. Additionally, rs2097432 should not be used as a surrogate for HLA-DQA1*05 testing for diverse populations. Ultimately, incorporating ancestry in personalized therapeutic approaches is important for treatment of Hispanic patients with IBD.</p>\",\"PeriodicalId\":10347,\"journal\":{\"name\":\"Clinical Gastroenterology and Hepatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.6000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Gastroenterology and Hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cgh.2024.07.032\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Gastroenterology and Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.cgh.2024.07.032","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Ancestral diversity in pharmacogenomics affects treatment for Hispanic/Latine populations with inflammatory bowel disease.
Background and aims: The prevalence of inflammatory bowel disease (IBD) among Hispanic/Latine communities is increasing. Pharmacogenomic studies reveal genetic markers that influence treatment decisions. The aim of our study was to examine the frequency and impact of genetic polymorphisms on thiopurine-associated leukopenia (NUDT15, TPMT) and anti-TNF immunogenicity (HLA-DQA1*05) in a cohort of Hispanic patients of diverse ancestral backgrounds.
Methods: We performed a multicenter, retrospective cohort study comprised of 2225 Hispanic participants. We measured the frequency of variation affecting drug response in NUDT15, TPMT, and HLA-DQA1*05, their ancestral origin (European, African, or Amerindian), and the rate of development of myelosuppression and immunogenicity to thiopurines and anti-TNFs, respectively, in exposed patients.
Results: NUDT15 and TPMT variants were rare, except for rs116855232 in NUDT15 which was common only in alleles of Amerindian origin. All NUDT15 variant alleles were inherited on an Amerindian haplotype, and among the Amerindian allele subset, the variant frequency of NUDT15*4 (rs147390019) was a remarkable 23% in patients with leukopenia but only 3% in patients without leukopenia. HLA-DQA1*05 and its European tagging variant rs2097432 were common in alleles from all ancestral origins and demonstrated association with immunogenicity to anti-TNFs. However, rs2097432 was only correlated with HLA-DQA1*05 in the European allele subset.
Conclusion: These findings indicate that NUDT15 testing should become standard clinical practice before prescribing thiopurines in individuals with Amerindian ancestry, including Hispanic individuals. Additionally, rs2097432 should not be used as a surrogate for HLA-DQA1*05 testing for diverse populations. Ultimately, incorporating ancestry in personalized therapeutic approaches is important for treatment of Hispanic patients with IBD.
期刊介绍:
Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion.
As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.