Risk genes and autoantibodies in Egyptian children with type 1 diabetes – low frequency of autoantibodies in carriers of the HLA‐DRB1*04:05‐DQA1*03‐DQB1*02 risk haplotype

El-Amir, Mostafa I; El-Feky, Mohamed A; Laine, Antti‐Pekka; Härkönen, Taina; El‐Badawy, Omnia; Eltayeb, Azza A.; ElMelegy, Tarek T; Knip, Mikael; Ilonen, Jorma

doi:10.1002/dmrr.2609

Cited by 14 publications

(22 citation statements)

References 33 publications

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“…The DRB1*04:05‐DQA1*03:02‐DQB1*02:02 (DR4‐DQ2) haplotype has also shown a positive association with T1D in this study (OR = 6.31; P c ‐value = .0326). This finding is in agreement with previous studies on Saudi, African American, and Egyptian populations 23,25,26 . This haplotype is very rare among most European‐derived populations, and the T1D Genetic Consortium could not demonstrate any significant difference 17 .…”

Section: Discussionsupporting

confidence: 93%

“…These haplotypes were previously reported to be susceptible to T1D among Saudis 23 . Similar findings were observed in European‐derived, African‐American, Arab, and Latino populations 16,17,25‐29 …”

Section: Discussionsupporting

confidence: 87%

“…However, DRB1*03:01‐DQA1*05:01‐DQB1*02:01 / DRB1*04:04‐DQA1*03:01‐DQB1*03:02 , which was reported to be positively associated with T1D in European‐derived and African American populations, 25,26 was rarely observed in Saudis and tended to be neutral in our data. Moreover, the DRB1*03:01‐DQB1*02:01 / DRB1*07:01‐DQB1*02:02 and DRB1*03:01‐DQB1*2:01 / DRB1*13:02‐DQB1*06:04 diplotypes were positively associated with T1D in African Americans, 25 but did not remain positively associated with T1D in Saudis after Bonferroni correction.…”

Section: Discussioncontrasting

confidence: 70%

“…DR3‐DQ2 / DR3‐DQ2, DR3‐DQ2 / DR4‐DQ8, DR3‐DQ2/DR4‐DQ2, DR4‐DQ2/DR4‐DQ2, and DR4‐DQ8 / DR4‐DQ8 diplotypes have been reported to be positively associated with T1D in different populations, including Caucasians, African Americans, and Arabs 17,26,30,53,54 . In contrast, homozygous DRB1*03:01‐DQA1*05:01‐DQB1*02:01 diplotype (DR3‐DQ2/ DR3‐DQ2) as well as combinations of the DRB1*03:01‐DQA1*05:01‐DQB1*02:01 haplotype and DRB1*04:01‐DQA1*03:01‐DQB1*03:02 , DRB1*04:02‐DQA1*03:01‐DQB1*03:02 , and DRB1*04:05‐DQA1*03:02‐DQB1*03:02 haplotypes (DR3‐DQ2/DR4‐DQ8 heterozygous diplotypes) were positively associated with T1D in Saudis.…”

Section: Discussionmentioning

confidence: 99%

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

Eltayeb‐Elsheikh

Khalil

Mubasher

et al. 2020

Diabetes Metabolism Res

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Aims Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA‐DRB1‐DQA1‐DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis. Methods A total of 222 children with T1D and 342 controls were genotyped for HLA‐DRB1, ‐DQA1, and ‐DQB1 using reverse sequence‐specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package. Results DRB1*03:01‐DQA1*05:01‐DQB1*02:01 (32.4%; OR = 3.68; Pc < .0001), DRB1*04:05‐DQA1*03:02‐DQB1*03:02 (6.6%; OR = 6.76; Pc < .0001), DRB1*04:02‐DQA1*03:01‐DQB1*03:02 (6.0%; OR = 3.10; Pc = .0194), DRB1*04:01‐DQA1*03:01‐DQB1*03:02 (3.7%; OR = 4.22; Pc = .0335), and DRB1*04:05‐DQA1*03:02‐DQB1*02:02 (2.7%; OR = 6.31; Pc = .0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01‐DQA1*02:01‐DQB1*02:02 (OR = 0.41; Pc = .0001), DRB1*13:01‐DQA1*01:03‐DQB1*06:03 (OR = 0.05; Pc < .0001), DRB1*15:01‐DQA1*01:02‐DQB1*06:02 (OR = 0.03; Pc < .0001), and DRB1*11:01‐DQA1*05:05‐DQB1*03:01 (OR = 0.07; Pc = .0291) were significantly decreased. Homozygous DRB1*03:01‐DQA1*05:01‐DQB1*02:01 genotypes and combinations of DRB1*03:01‐DQA1*05:01‐DQB1*02:01 with DRB1*04:05‐DQA1*03:02‐DQB1*03:02, DRB1*04:02‐DQA1*03:01‐DQB1*03:02, and DRB1*04:01‐DQA1*03:01‐DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01‐DQA1*05:01‐DQB1*02:01 with DRB1*07:01‐DQA1*02:01‐DQB1*02:02 and DRB1*13:02‐DQA1*01:02‐DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction. Conclusions HLA‐DRB1‐DQA1‐DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle‐Eastern populations but are quite different than those of East Asians.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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

Eltayeb‐Elsheikh

Khalil

Mubasher

et al. 2020

Diabetes Metabolism Res

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“…These results suggest that, even when using age-appropriate comparisons, the proportion of diabetes resulting from autoimmunity in sub-Saharan Africa may be lower than in the European population. Recent reports from Cameroon [ 8 ], Tunisia [ 29 ] and Egypt [ 30 ] have drawn attention to the influence of HLA status on autoantibody production in T1DM in these countries. In regions where there are lower frequencies of diabetes-associated HLA haplotypes, there may be fewer cases of diabetes with an autoimmune basis, although this is unlikely to be the only factor.…”

Section: Islet-cell Autoimmunity In Sub-saharan Africamentioning

confidence: 99%

Type 1 Diabetes in a Resource-Poor Setting: Malnutrition Related, Malnutrition Modified, or Just Diabetes?

2018

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Purpose of ReviewVery little is known about the occurrence of type 1 diabetes (T1DM) in resource-poor countries and particularly in their rural hinterlands.Recent FindingsStudies of the epidemiology of T1DM in Ethiopia and similar countries in sub-Saharan Africa show that the pattern of presenting disease differs substantially from that in the West. Typically, the peak age of onset of the disease is more than a decade later with a male excess and a low prevalence of indicators of islet-cell autoimmunity. It is also associated with markers of undernutrition.SummaryThese findings raise the question as to whether the principal form of T1DM seen in these resource-poor communities has a different pathogenesis. Whether the disease is a direct result of malnutrition or whether malnutrition may modify the expression of islet-cell autoimmunity is unclear. However, the poor prognosis in these settings underlines the urgent need for detailed clinical and epidemiological studies.

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Genetic Epidemiology of Type 1 Diabetes in the 22 Arab Countries

Zayed

2016

Curr Diab Rep

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Type 1 diabetes (T1D) is a complex autoimmune disorder that results from the T cell-mediated destruction of the pancreatic β cells and is due to interactions between environmental and genetic factors. Although Arabs have one of the highest global incidence and prevalence rates of T1D, unfortunately, there is a dearth of information regarding the genetic epidemiology of T1D in the Arab world. Arabs share several HLA haplotypes with other ethnic groups, which confer either susceptibility or protection to T1D, but they have specific haplotypes that are distinctive from other ethnicities. Among different Arab countries, several non-HLA genes were reported to be associated with susceptibility to T1D, including CTLA4, CD28, PTPN22, TCRβ, CD3z, IL15, BANK1, and ZAP70. In Arab countries, consanguinity, endogamy, and first-cousin marriage rates are some of the highest reported worldwide and are responsible for the creation of several inbreeding communities within the Arab world that have led to an increase in homozygosity of both the HLA haplotypes and non-HLA genes associated with either protection or susceptibility to T1D among Arabs. Homozygosity reduces the HLA complexity and is expected to facilitate our understanding of the mode of inheritance of HLA haplotypes and provide valuable insight into the intricate genotype-phenotype correlations in T1D patients. In this review, based on literature studies, I will discuss the current epidemiological profile and molecular genetic risks of Arabs with T1D.

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Risk genes and autoantibodies in Egyptian children with type 1 diabetes – low frequency of autoantibodies in carriers of the HLA‐DRB104:05‐DQA103‐DQB1*02 risk haplotype

Abstract: Besides a strong HLA-DR3-DQ2 association, a relatively high frequency of the DR4-DQ2 haplotype characterized the diabetic population. The low frequency of autoantibodies in children with HLA-DR4-DQ2 may indicate specific pathogenetic pathways associated with this haplotype.

Cited by 14 publications

References 33 publications

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

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

Type 1 Diabetes in a Resource-Poor Setting: Malnutrition Related, Malnutrition Modified, or Just Diabetes?

Genetic Epidemiology of Type 1 Diabetes in the 22 Arab Countries

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