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. 2023 Apr 27;14(5):991.
doi: 10.3390/genes14050991.

Association between HLA Class II Alleles/Haplotypes and Genomic Ancestry in Brazilian Patients with Type 1 Diabetes: A Nationwide Exploratory Study

Marília Brito Gomes  1 , Vandilson Rodrigues  2 , Deborah Conte Santos  1 , Paulo Ricardo Villas Bôas  3 , Dayse A Silva  4 , Rossana Santiago de Sousa Azulay  2   5 , Sergio Atala Dib  6 , Elizabeth João Pavin  7 , Virgínia Oliveira Fernandes  8   9   10 , Renan Magalhães Montenegro Junior  8   9   10 , João Soares Felicio  11 , Rosangela Réa  12 , Carlos Antonio Negrato  13 , Luís Cristóvão Porto  3
Affiliations

Association between HLA Class II Alleles/Haplotypes and Genomic Ancestry in Brazilian Patients with Type 1 Diabetes: A Nationwide Exploratory Study

Marília Brito Gomes et al. Genes (Basel). .

Abstract

We aimed to identify HLA-DRB1, -DQA1, and -DQB1 alleles/haplotypes associated with European, African, or Native American genomic ancestry (GA) in admixed Brazilian patients with type 1 diabetes (T1D). This exploratory nationwide study enrolled 1599 participants. GA percentage was inferred using a panel of 46 ancestry informative marker-insertion/deletion. Receiver operating characteristic curve analysis (ROC) was applied to identify HLA class II alleles related to European, African, or Native American GA, and showed significant (p < 0.05) accuracy for identifying HLA risk alleles related to European GA: for DRB1*03:01, the area under the curve was (AUC) 0.533; for DRB1*04:01 AUC = 0.558, for DRB1*04:02 AUC = 0.545. A better accuracy for identifying African GA was observed for the risk allele DRB1*09:01AUC = 0.679 and for the protective alleles DRB1*03:02 AUC = 0.649, DRB1*11:02 AUC = 0.636, and DRB1*15:03 AUC = 0.690. Higher percentage of European GA was observed in patients with risk haplotypes (p < 0.05). African GA percentage was higher in patients with protective haplotypes (p < 0.05). Risk alleles and haplotypes were related to European GA and protective alleles/haplotypes to African GA. Future studies with other ancestry markers are warranted to fill the gap in knowledge regarding the genetic origin of T1D in highly admixed populations such as that found in Brazil.

Keywords: HLA; admixed; ethnicity; genomic ancestry; human leukocyte antigen; type 1 diabetes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of studied patients with type 1 diabetes.
Figure 2
Figure 2
Descriptive analysis of global genomic ancestry percentage in a Brazilian sample of patients with type 1 diabetes. (a) Mean and standard deviation of European, African, and Native American ancestry percentage. (b) Individual global ancestry sorted in ascending order of European ancestry percentage. (c) Distribution of European, African, and Native American ancestry percentages sorted in different cutoff categories.
Figure 3
Figure 3
Distribution of allele frequency of HLA class II in Brazilian patients with type 1 diabetes (2n = 3198). (a) Allele frequency of HLA-DRB1. (b) Allele frequency of HLA-DQA1. (c) Allele frequency of HLA-DQB1.
Figure 4
Figure 4
HLA class II alleles associated with increased percentage of European, African, or Native American genomic ancestry in the Brazilian patients with type 1 diabetes (p < 0.05 in AUC analysis).
Figure 5
Figure 5
Distribution of risk (a) and protective (b) haplotypes for patients with type 1 diabetes (n = 1599).
See this image and copyright information in PMC

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