Jamila A Perini, Alessandra S Dias, Leonor Gusmão, Larissa B Skaf, Anna Beatriz R Elias, Paulo C Basta, Marcelo A Carvalho, Guilherme Suarez-Kurtz
{"title":"巴西亚马逊地区土著人UGT1A1多态性和代谢表型","authors":"Jamila A Perini, Alessandra S Dias, Leonor Gusmão, Larissa B Skaf, Anna Beatriz R Elias, Paulo C Basta, Marcelo A Carvalho, Guilherme Suarez-Kurtz","doi":"10.1097/FPC.0000000000000566","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.</p><p><strong>Methods: </strong>Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes.</p><p><strong>Results: </strong>All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes.</p><p><strong>Conclusion: </strong>This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant ( UGT1A1 * 80 ) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"153-158"},"PeriodicalIF":1.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"UGT1A1 polymorphisms and metabolic phenotypes in indigenous peoples from the Brazilian Amazon.\",\"authors\":\"Jamila A Perini, Alessandra S Dias, Leonor Gusmão, Larissa B Skaf, Anna Beatriz R Elias, Paulo C Basta, Marcelo A Carvalho, Guilherme Suarez-Kurtz\",\"doi\":\"10.1097/FPC.0000000000000566\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.</p><p><strong>Methods: </strong>Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes.</p><p><strong>Results: </strong>All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes.</p><p><strong>Conclusion: </strong>This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant ( UGT1A1 * 80 ) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.</p>\",\"PeriodicalId\":19763,\"journal\":{\"name\":\"Pharmacogenetics and genomics\",\"volume\":\" \",\"pages\":\"153-158\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenetics and genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FPC.0000000000000566\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenetics and genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000566","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/11 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
UGT1A1 polymorphisms and metabolic phenotypes in indigenous peoples from the Brazilian Amazon.
Objectives: To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.
Methods: Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes.
Results: All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes.
Conclusion: This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant ( UGT1A1 * 80 ) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.
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Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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