Association of <scp><i>HLA‐DR‐DQ</i></scp> alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis

Eltayeb‐Elsheikh, Nezar; Khalil, Eltahir Awad Gasim; Mubasher, Mohamed; Al-jurayyan, Abdullah; Alharthi, Hanan; Omer, Waleed H; ElGhazali, Inas; Sherbeeni, Suphia M.; AlGhofely, Mohammed A.; Ilonen, Jorma; ElGhazali, Geyhad

doi:10.1002/dmrr.3345

Cited by 5 publications

(12 citation statements)

References 52 publications

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“…Higher frequencies of DRB1*03 and DRB1*04 were observed among T1D patients with odd ratios 2.7 and 10.8, respectively, and are a strong risk factor; whereas, DRB1*07, DRB1*13 and DRB1*15 had lower frequencies with odd ratios 0.3, 0.3 and 0.1, respectively, and acted as protective factors against T1D. Our results confirm data of Nezar et al in a recent Saudi study (Eltayeb‐Elsheikh et al., 2020).…”

Section: Discussionsupporting

confidence: 91%

“…Association of HLA with T1D has been studied worldwide and in Saudi Arabia (Ei Wafai et al., 2011; Eltayeb‐Elsheikh et al., 2020); however, to the best of our knowledge, no study has combined the HLA genes with the SNPs we genotyped in this study. Higher frequencies of DRB1*03 and DRB1*04 were observed among T1D patients with odd ratios 2.7 and 10.8, respectively, and are a strong risk factor; whereas, DRB1*07, DRB1*13 and DRB1*15 had lower frequencies with odd ratios 0.3, 0.3 and 0.1, respectively, and acted as protective factors against T1D.…”

Section: Discussionmentioning

confidence: 99%

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Association of single‐nucleotide polymorphisms in tumour necrosis factor and human leukocyte antigens genes with type 1 diabetes

Osman

Brema

AlQurashi

et al. 2021

Int J Immunogenetics

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Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive destruction of insulin‐producing pancreatic beta cells. This multifactorial disease has a strong genetic component associated with the human leukocyte antigens (HLA) and non‐HLA regions. In this study, we compared frequencies of HLA‐DRB1 alleles and single‐nucleotide polymorphisms (SNPs) associated the genes coding for: toll‐like receptors (TLRs), tumour necrosis factor (TNF), interleukin‐1 (IL‐1), interleukin‐1 receptor type 1 (IL‐1R1), interleukin‐1 receptor antagonist (IL‐1RN), interleukin‐2 (IL‐2) and interleukin‐12B (IL‐12B), between T1D patients and healthy controls. The aim was to identify frequency differences and linkage between these genetic markers in T1D patients and healthy controls. Twelve SNPs were investigated as follows: rs16944 (IL‐1B), rs1143634 (IL‐1B), rs1800587 (IL‐1A), rs2069762 (IL‐2), rs3212227 (IL‐12B), rs2234650 (IL‐1R1), rs315952 (IL‐1RN), rs3804099 (TLR2), rs4986790 (TLR4), rs4986791 (TLR4), rs1800629 (TNF) and rs361525 (TNF). TaqMan genotype assay method was used for SNPs genotyping. HLA‐DRB1* genes were typed by Sequence Specific Oligonucleotide Probe (SSOP). SPSS and SNPStats programs were used for the statistical analysis. Significant differences between T1D and control groups were found for the dominant model of rs361525 and rs1800629A:rs361525G genotypes for TNF. Increased frequencies of DRB1*03 and DRB1*04 and decreased frequencies of DRB1*07, DRB1*11 and DRB1*13 and DRB1*15 were observed in T1D patients compared with controls. However, the genotype, DRB1*07 with rs1800629A/G was associated with T1D. We have confirmed that DRB1*03 and DRB1*04 are associated with increased risk and DRB1*07, DRB1*11 and DRB1*13 and DRB1*15 with decreased risk of T1D. Also, the dominant model of rs361525A, and the rs1800629G:361525A genotype were associated with increased risk. The simultaneous presence of DRB1*07 and rs1800629A/G genotypes in 23 out of 27 DRB1*07 positive T1D patients implied that islet cell peptide processing may have been biased towards autoimmunity by upregulation of TNF associated intronic SNPs.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Association of single‐nucleotide polymorphisms in tumour necrosis factor and human leukocyte antigens genes with type 1 diabetes

Osman

Brema

AlQurashi

et al. 2021

Int J Immunogenetics

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“…The HLA contribution to T1D genetic susceptibility differs between populations and ethnic groups ( Noble et al, 2013 ), largely due to varied frequencies and functional associations of DRB1 and DQB1 alleles and haplotypes (susceptible, protective). Key DRB1 and DQB1 alleles and haplotypes associated with T1D were reported for Caucasian and non-Caucasian populations ( Petrone et al, 2001 ; Erlich et al, 2008 ; Ilonen et al, 2009 ; Noble et al, 2013 ), which included DRB1*03:01 , DRB1*04:02, DRB1*04:05, DQB1*02:01, and DQB1*03:02 along with DRB1*03:01 ∼DQB1*02:01 (DR3), DRB1*04:02∼DQB1*03:02 (DR4), and DRB1*04:05∼DQB1*03:02 haplotypes also observed in this study and studies on other Arab populations from Bahrain, Tunisia, Lebanon and Saudi Arabia ( Al-Harbi et al, 2004 ; Al-Jenaidi et al, 2005 ; Stayoussef et al, 2009 ; Manan et al, 2010 ; El-Amir et al, 2015 ; Eltayeb-Elsheikh et al, 2020 ). It is noteworthy that no DR3 or DR4 haplotype linked with T1D was detected in East and Southeast Asians ( Hashimoto et al, 1994 ; Kawabata et al, 2002 ).…”

Section: Discussionsupporting

confidence: 86%

HLA-DRB1 and –DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations

et al. 2022

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Background: HLA class II (DR and DQ) alleles and antigens have historically shown strong genetic predisposition to type 1 diabetes (T1D). This study evaluated the association of DRB1 and DQB1 alleles, genotypes, and haplotypes with T1D in United Arab Emirates.Materials and Methods: Study subjects comprised 149 patients with T1D, and 147 normoglycemic control subjects. Cases and controls were Emiratis and were HLA-DRB1 and -DQB1 genotyped using sequence-based typing. Statistical analysis was performed using Bridging Immunogenomic Data-Analysis Workflow Gaps R package.Results: In total, 15 DRB1 and 9 DQB1 alleles were identified in the study subjects, of which the association of DRB1*03:01, DRB1*04:02, DRB1*11:01, DRB1*16:02, and DQB1*02:01, DQB1*03:02, DQB1*03:01, and DQB1*06:01 with altered risk of T1D persisted after correcting for multiple comparisons. Two-locus haplotype analysis identified DRB1*03:01∼DQB1*02:01 [0.44 vs. 0.18, OR (95% CI) = 3.44 (2.33–5.1), Pc = 3.48 × 10−10]; DRB1*04:02∼DQB1*03:02 [0.077 vs. 0.014, OR = 6.06 (2.03–24.37), Pc = 2.3 × 10−3] and DRB1*04:05∼DQB1*03:02 [0.060 vs. 0.010, OR = 6.24 (1.79–33.34), Pc = 0.011] as positively associated, and DRB1*16:02∼DQB1*05:02 [0.024 vs. 0.075, OR = 0.3 (0.11–0.74), Pc = 0.041] as negatively associated with T1D, after applying Bonferroni correction. Furthermore, the highest T1D risk was observed for DR3/DR4 [0.104 vs. 0.006, OR = 25.03 (8.23–97.2), Pc = 2.6 × 10−10], followed by DR3/DR3 [0.094 vs. 0.010, OR = 8.72 (3.17–25.32), Pc = 3.18 × 10−8] diplotypes.Conclusion: While DRB1 and DQB1 alleles and haplotypes associated with T1D in Emiratis showed similarities to Caucasian and non-Caucasian populations, several alleles and haplotypes associated with T1D in European, African, and Asian populations, were not observed. This underscores the contribution of ethnic diversity and possible diverse associations between DRB1 and DQB1 and T1D across different populations.

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“…The highest risk of T1D was seen in individuals who carry the DRB1*03:01-DQB1*02:01/DRB1*04:02/05-DQB1*03:02 diplotype in Emiratis ( 27 ). While HLA class II alleles and haplotypes detected in individuals with T1D belonging to the Saudi Arabian and Omani populations were consistent to those in Caucasians and other Middle Eastern populations ( 28 , 29 ).…”

Section: Introductionsupporting

confidence: 69%

Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children

Dashti,

Nizam,

Jacob

et al. 2023

Front. Immunol.

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Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts.

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Association of HLA‐DR‐DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis

Cited by 5 publications

References 52 publications

Association of single‐nucleotide polymorphisms in tumour necrosis factor and human leukocyte antigens genes with type 1 diabetes

Association of single‐nucleotide polymorphisms in tumour necrosis factor and human leukocyte antigens genes with type 1 diabetes

HLA-DRB1 and –DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations

Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children

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