Segregation Analysis of Genotyped and Family-Phased, Long Range MHC Classical Class I and Class II Haplotypes in 5 Families With Type 1 Diabetes Proband in the United Arab Emirates

Tay, Guan K.; Naqbi, Halima Al; Mawart, Aurélie; Baalfaqih, Zahrah; Almaazmi, Anoud; Deeb, Asma; Alsafar, Habiba

doi:10.3389/fgene.2021.670844

Cited by 6 publications

(3 citation statements)

References 56 publications

(87 reference statements)

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“…Families were approached and briefed on the study and invited to participate. The cohort also included a subset of five families that have been previously published by Tay, et al 35 . Those families included healthy parents and at least one child with Type 1 Diabetes.…”

Section: Methodsmentioning

confidence: 99%

Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates

Alnaqbi

Tay

Chehadeh

et al. 2022

Sci Rep

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Aside from its anthropological relevance, the characterization of the allele frequencies of genes in the human Major Histocompatibility Complex (MHC) and the combination of these alleles that make up MHC conserved extended haplotypes (CEHs) is necessary for histocompatibility matching in transplantation as well as mapping disease association loci. The structure and content of the MHC region in Middle Eastern populations remain poorly characterized, posing challenges when establishing disease association studies in ethnic groups that inhabit the region and reducing the capacity to translate genetic research into clinical practice. This study was conceived to address a gap of knowledge, aiming to characterize CEHs in the United Arab Emirates (UAE) population through segregation analysis of high-resolution, pedigree-phased, MHC haplotypes derived from 41 families. Twenty per cent (20.5%) of the total haplotype pool derived from this study cohort were identified as putative CEHs in the UAE population. These consisted of CEHs that have been previously detected in other ethnic groups, including the South Asian CEH 8.2 [HLA- C*07:02-B*08:01-DRB1*03:01-DQA1*05:01-DQB1*02:01 (H.F. 0.094)] and the common East Asian CEH 58.1 [HLA- C*03:02-B*58:01-DRB1*03:01- DQA1*05:01-DQB1*02:01 (H.F. 0.024)]. Additionally, three novel CEHs were identified in the current cohort, including HLA- C*15:02-B*40:06-DRB1*16:02-DQB1*05:02 (H.F. 0.035), HLA- C*16:02-B*51:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.029), and HLA- C*03:02-B*58:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.024). Overall, the results indicate a substantial gene flow with neighbouring ethnic groups in the contemporary UAE population including South Asian, East Asian, African, and European populations. Importantly, alleles and haplotypes that have been previously associated with autoimmune diseases (e.g., Type 1 Diabetes) were also present. In this regard, this study emphasizes that an appreciation for ethnic differences can provide insights into subpopulation-specific disease-related polymorphisms, which has remained a difficult endeavour.

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Section: Methodsmentioning

confidence: 99%

Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates

Alnaqbi

Tay

Chehadeh

et al. 2022

Sci Rep

Self Cite

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“…Since HLA-B8 is often linked with HLA-DR3 representing a conserved haplotype and is not considered per se as a risk factor for developing T1D (8,(18)(19)(20), we analyzed the contribution of HLA-DR3 or HLA-DR4 matching only. Of 1403 islet recipients, we excluded 281 islet-kidney recipients (islets after kidney, simultaneous islet kidney, and kidney after islet), 711 recipients who received a 2 nd islet infusion, 111 recipients with no outcomes reported at years 1-5 post-transplant, and 213 recipients with incomplete HLA-DR data reporting (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Matching for HLA-DR excluding diabetogenic HLA-DR3 and HLA-DR4 predicts insulin independence after pancreatic islet transplantation

Ballou¹,

Barton²,

Payne³

et al. 2023

Front. Immunol.

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IntroductionIn pancreatic islet transplantation, the exact contribution of human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets may be exposed to allogenic rejection but also the recurrence of type 1 diabetes (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic HLA-DR3 or HLA-DR4 matches.MethodsWe retrospectively examined the HLA profile in 965 transplant recipients and 2327 islet donors. The study population was obtained from patients enrolled in the Collaborative Islet Transplant Registry. We then identified 87 recipients who received a single-islet infusion. Islet-kidney recipients, 2nd islet infusion, and patients with missing data were excluded from the analysis (n=878).ResultsHLA-DR3 and HLA-DR4 were present in 29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group A), 11 with 1 or 2 HLA-DR-matches but excluding HLA-DR3 and HLA- DR4 (group B), and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was maintained in a significantly higher percentage of group B recipients from year one through five post-transplantation (p<0.01). At five-year post-transplantation, 78% of group B was insulin-independent compared to 24% (group A) and 35% (group C). Insulin-independence correlated with significantly better glycemic control (HbA1c <7%), fasting blood glucose, and reduced severe hypoglycemic events. Matching HLA-A-B-DR (≥3) independently of HLA- DR3 or HLA-DR4 matching did not improve graft survival.ConclusionThis study suggests that matching HLA-DR but excluding the diabetogenic HLA-DR3 and/or 4 is a significant predictor for long-term islet survival.

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“…How do these conserved sequences do what they do? Some of these questions are being addressed by Okano et al (2020), Kulski et al (2021a), Kulski et al (2021b), Cun et al (2021), andTay et al (2021). These groups are discovering new mechanisms of gene regulation embedded within the non-coding regions of Ancestral Haplotypes.…”

Section: Conserved Polymorphic Sequencesmentioning

confidence: 99%

Commentary: Conserved polymorphic sequences protect themselves for future challenges

Dawkins

Lloyd

2022

Front. Genet.

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Segregation Analysis of Genotyped and Family-Phased, Long Range MHC Classical Class I and Class II Haplotypes in 5 Families With Type 1 Diabetes Proband in the United Arab Emirates

Cited by 6 publications

References 56 publications

Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates

Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates

Matching for HLA-DR excluding diabetogenic HLA-DR3 and HLA-DR4 predicts insulin independence after pancreatic islet transplantation

Commentary: Conserved polymorphic sequences protect themselves for future challenges

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