HLA-A, -B, -Cw, -DQA1, -DQB1 and -DRB1 alleles in a population from the Azores

Armas, José Manzano de; Couto, Rowena Rubim; Santos, Maria de Fatima Maciel dos; Bettencourt, Bruno Filipe

doi:10.1016/j.humimm.2004.08.006

Cited by 2 publications

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“…Strikingly, the DRB1*04:08 allele was significantly associated with EOT1D but not with LaOT1D ( Figure 2B and Supplementary Table 3 ). Consistent with earlier findings in Portuguese ( 35 , 36 ) and Spanish cohorts ( 37 ), the DRB1*04:08 allele was found at a remarkably low frequency in nondiabetic controls (0.3%, Supplementary Table 3 ). Conversely, we found that the classical T1D risk allele DRB1*04:05 was associated with LaOT1D while it was absent in the EOT1D cohort.…”

Section: Resultssupporting

confidence: 90%

The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population

Caramalho,

Matoso,

Ligeiro

et al. 2024

Front. Immunol.

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IntroductionEarly-onset Type 1 diabetes (EOT1D) is considered a disease subtype with distinctive immunological and clinical features. While both Human Leukocyte Antigen (HLA) and non-HLA variants contribute to age at T1D diagnosis, detailed analyses of EOT1D-specific genetic determinants are still lacking. This study scrutinized the involvement of the HLA class II locus in EOT1D genetic control.MethodsWe conducted genetic association and regularized logistic regression analyses to evaluate genotypic, haplotypic and allelic variants in DRB1, DQA1 and DQB1 genes in children with EOT1D (diagnosed at £5 years of age; n=97), individuals with later-onset disease (LaOT1D; diagnosed 8-30 years of age; n=96) and nondiabetic control subjects (n=169), in the Portuguese population.ResultsAllelic association analysis of EOT1D and LaOT1D unrelated patients in comparison with controls, revealed that the rare DRB1*04:08 allele is a distinctive EOT1D susceptibility factor (corrected p-value=7.0x10-7). Conversely, the classical T1D risk allele DRB1*04:05 was absent in EOT1D children while was associated with LaOT1D (corrected p-value=1.4x10-2). In corroboration, HLA class II haplotype analysis showed that the rare DRB1*04:08-DQ8 haplotype is specifically associated with EOT1D (corrected p-value=1.4x10-5) and represents the major HLA class II genetic driver and discriminative factor in the development of early onset disease.DiscussionThis study uncovered that EOT1D holds a distinctive spectrum of HLA class II susceptibility loci, which includes risk factors overlapping with LaOT1D and discriminative genetic configurations. These findings warrant replication studies in larger multicentric settings encompassing other ethnicities and may impact target screening strategies and follow-up of young children with high T1D genetic risk as well as personalized therapeutic approaches.

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Section: Resultssupporting

confidence: 90%

The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population

Caramalho,

Matoso,

Ligeiro

et al. 2024

Front. Immunol.

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HLA class I and II polymorphisms in Azores show different settlements in Oriental and Central islands

Spínola¹,

Brehm²,

Bettencourt³

et al. 2005

Tissue Antigens

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Human leucocyte antigen-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 polymorphisms were examined in the Azorean population. The data were obtained at high-resolution level, using polymerase chain reaction (PCR) with sequence-specific primer, PCR-sequence-specific oligonucleotides and sequence-based typing. The most frequent allele in each locus was: A*0201 (24.5%), B*510101 (9.8%), Cw*0401 (14.8%), DRB1*070101 (18.3%), DQA1*0201 (17.4%) and DQB1*0301 (19.4%). The predominant extended haplotype was A*0202-B*1503-Cw*0202-DRB1*090102-DQA1*0303- DQB1*0202 (1.9%), which was found to be absent in the Portuguese mainland. The present study corroborates historical sources that say the Azores were populated not only by Portuguese but also by other Europeans, mostly Flemish people. Despite dendrogram analysis showing some remote Asian genetic affinities, the lack of specific alleles and haplotypes from those populations does not allow us to conclude for direct influence. Haplotype and allele frequencies in Azores show no homogeneous distribution between Oriental and Central islands of this archipelago. The Oriental islands harbour several haplotypes already found in mainland Portugal and identified as Mediterranean and European. The Central group of islands on the contrary clearly shows an influence of north Europeans (most probably derived from a well-documented Flemish settlement), with much less affinity to mainland Portugal.

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HLA-A, -B, -Cw, -DQA1, -DQB1 and -DRB1 alleles in a population from the Azores

Cited by 2 publications

References 0 publications

The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population

The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population

HLA class I and II polymorphisms in Azores show different settlements in Oriental and Central islands

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