Marília Brito Gomes, Gilson Costa dos Santos Jr, Rossana Santiago de Sousa Azulay, Deborah Conte Santos, Dayse Aparecida Silva, Paulo Ricardo Vilas Boas Carvalho, Carlos Antonio Negrato, Luís Cristóvão Porto
{"title":"巴西混血人群中 HLA 等位基因和单倍型与 1 型糖尿病确诊年龄的关系:一项全国性研究。","authors":"Marília Brito Gomes, Gilson Costa dos Santos Jr, Rossana Santiago de Sousa Azulay, Deborah Conte Santos, Dayse Aparecida Silva, Paulo Ricardo Vilas Boas Carvalho, Carlos Antonio Negrato, Luís Cristóvão Porto","doi":"10.1111/tan.15574","DOIUrl":null,"url":null,"abstract":"<p>To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6–<11 years, ≥11–<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self-reported colour–race and identified a familiar history of T1D in first-degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub-Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as <i>HLA-DQB1*03:02g</i>, <i>-DQA1*03:01g</i>, <i>-02:01g</i>, <i>DRB1*04:05g</i> and -<i>04:02g</i> were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as <i>DRB1*07:01g</i>, <i>-13:03g</i>, <i>DQB1*06:02g</i> and <i>DQA1*02:01</i> were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self-reported colour–race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype <i>DRB1*03:01g~DQA1*05:01g~DQB1*02:01g</i> did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high-risk haplotype <i>DRB1*04:05~DQA1*03:01~DQB1*03:02</i> was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles <i>DQA1*01:02g</i>, <i>DQB1*06:02</i>g, <i>DRB1*07:01g</i> and <i>DRB1*13:03g</i> and haplotypes <i>DRB1*13:03g~DQA1*05:01g~DQB1*03:01g</i> and <i>DRB1*16:02g~DQA1*01:02g~DQB1*05:02g</i> were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well-known genomic risk or protection factors for T1D.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association between HLA alleles and haplotypes with age at diagnosis of type 1 diabetes in an admixed Brazilian population: A nationwide study\",\"authors\":\"Marília Brito Gomes, Gilson Costa dos Santos Jr, Rossana Santiago de Sousa Azulay, Deborah Conte Santos, Dayse Aparecida Silva, Paulo Ricardo Vilas Boas Carvalho, Carlos Antonio Negrato, Luís Cristóvão Porto\",\"doi\":\"10.1111/tan.15574\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6–<11 years, ≥11–<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self-reported colour–race and identified a familiar history of T1D in first-degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub-Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as <i>HLA-DQB1*03:02g</i>, <i>-DQA1*03:01g</i>, <i>-02:01g</i>, <i>DRB1*04:05g</i> and -<i>04:02g</i> were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as <i>DRB1*07:01g</i>, <i>-13:03g</i>, <i>DQB1*06:02g</i> and <i>DQA1*02:01</i> were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self-reported colour–race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype <i>DRB1*03:01g~DQA1*05:01g~DQB1*02:01g</i> did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high-risk haplotype <i>DRB1*04:05~DQA1*03:01~DQB1*03:02</i> was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles <i>DQA1*01:02g</i>, <i>DQB1*06:02</i>g, <i>DRB1*07:01g</i> and <i>DRB1*13:03g</i> and haplotypes <i>DRB1*13:03g~DQA1*05:01g~DQB1*03:01g</i> and <i>DRB1*16:02g~DQA1*01:02g~DQB1*05:02g</i> were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well-known genomic risk or protection factors for T1D.</p>\",\"PeriodicalId\":13172,\"journal\":{\"name\":\"HLA\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-07-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"HLA\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/tan.15574\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"HLA","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/tan.15574","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Association between HLA alleles and haplotypes with age at diagnosis of type 1 diabetes in an admixed Brazilian population: A nationwide study
To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6–<11 years, ≥11–<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self-reported colour–race and identified a familiar history of T1D in first-degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub-Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as HLA-DQB1*03:02g, -DQA1*03:01g, -02:01g, DRB1*04:05g and -04:02g were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as DRB1*07:01g, -13:03g, DQB1*06:02g and DQA1*02:01 were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self-reported colour–race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype DRB1*03:01g~DQA1*05:01g~DQB1*02:01g did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high-risk haplotype DRB1*04:05~DQA1*03:01~DQB1*03:02 was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles DQA1*01:02g, DQB1*06:02g, DRB1*07:01g and DRB1*13:03g and haplotypes DRB1*13:03g~DQA1*05:01g~DQB1*03:01g and DRB1*16:02g~DQA1*01:02g~DQB1*05:02g were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well-known genomic risk or protection factors for T1D.
期刊介绍:
HLA, the journal, publishes articles on various aspects of immunogenetics. These include the immunogenetics of cell surface antigens, the ontogeny and phylogeny of the immune system, the immunogenetics of cell interactions, the functional aspects of cell surface molecules and their natural ligands, and the role of tissue antigens in immune reactions. Additionally, the journal covers experimental and clinical transplantation, the relationships between normal tissue antigens and tumor-associated antigens, the genetic control of immune response and disease susceptibility, and the biochemistry and molecular biology of alloantigens and leukocyte differentiation. Manuscripts on molecules expressed on lymphoid cells, myeloid cells, platelets, and non-lineage-restricted antigens are welcomed. Lastly, the journal focuses on the immunogenetics of histocompatibility antigens in both humans and experimental animals, including their tissue distribution, regulation, and expression in normal and malignant cells, as well as the use of antigens as markers for disease.