Type 1 diabetes and the HLA-D locus

Sachs, J. A.; Cudworth, A G; Jaraquemada, Dolores; Gorsuch, A.N.; Festenstein, H.

doi:10.1007/bf01228300

Cited by 63 publications

(33 citation statements)

References 5 publications

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“…A number of other characteristics reinforced this, including male predominance, which is characteristic of Type I diabetes in young adult life [30], and which would also be expected in this cohort because affected fathers are more likely than affected mothers to transmit diabetes to their offspring. The increased frequency of HLA DRB1*03-DQA1*0501-DQB1*0201 / DRB1*04- DQA1*0301-DQB1*0302, the strongest susceptibility genotype for Type I diabetes [31], also supports the classification (Table 2). Although Type II diabetes was largely a diagnosis of exclusion, most of the individuals in this category were also overweight.…”

Section: Discussionsupporting

confidence: 61%

Diabetes in the parents of children with Type I diabetes

et al. 2002

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It has long been noted that late onset diabetes is common in the parents and siblings of individuals who develop diabetes before the age of 30 [1]. In keeping with this, later studies have shown an apparent overlap between Type I and Type II diabetes in these families [2±7]. Type II diabetes has been observed more often in relatives of individuals with Type I diabetes than in control groups [3,4], and siblings of children with Type I diabetes are more likely to be affected if a parent has Type II diabetes [5,6]. An overlap between Type I and Type II diabetes was also suggested by a study of probands with Type II diabetes in which those with a family history of Type I diabetes showed a phenotype more characteristic of Type I diabetes [7]. These observations indicate a genetic link between Type I and Type II diabetes but the method of phenotyping used in previous studies requires further consideration.Classification of diabetes by treatment [8,9] has now been superseded by classification according to cause [10,11]. As a result, it is now recognised that Diabetologia (2002) Abstract Aims/hypothesis. Previous studies have reported an excess of Type II (non-insulin-dependent) diabetes mellitus in parents of children with Type I (insulindependent) diabetes mellitus. We set out to characterise the clinical and immunogenetic features of diabetes in parents of affected children, and to test the hypothesis that there is no excess of Type II diabetes within this population. Methods. Clinical details were collected from 3164 parents of 1641 children with Type I diabetes participating in the Bart's-Oxford study of childhood diabetes. Islet cell antibodies, antibodies to GAD and IA-2, and HLA class II genotype were determined in a subset of this group. Individuals were assigned a classification of Type I diabetes on the basis of clinical features and measurement of islet autoantibodies. Results. Of 184 parents with diabetes, 138 (75 %) were on insulin. At least one islet autoantibody was detected in 90 (59 %) of 152 parents tested, and of 116 who were HLA-typed, 23 (20 %) had the highest risk genotype HLA-DRB1*03-DQA1*0501-DQB1*0201 / DRB1*04-DQA1*0301-DQB1*0302. Of 46 non-insulin-treated parents, 12 had islet autoantibodies. Of all parents, 141 (4.5 %) were therefore classified as having Type I diabetes, and 31 (0.98 %) as Type II diabetes; 12 could not be classified because of missing data or samples. Conclusion/interpretation. Autoimmune diabetes can present late and without immediate need for insulin treatment in parents of children with the disease. Previous studies have categorised this as Type II diabetes. Our study suggests that there is no excess of non-autoimmune diabetes in the families of children with Type I diabetes. [Diabetologia (2002) 45:495±501]

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Section: Discussionsupporting

confidence: 61%

Diabetes in the parents of children with Type I diabetes

et al. 2002

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“…This is of particular interest because HLA-DR4 (and DW4) is associated with both rheumatoid arthritis and type I diabetes, although in the latter it may be a relatively weak susceptibility factor in the absence of HLA-DW3-DR3. 17 In conclusion, this study has provided strong evidence for the existence of more than one susceptibility gene in the majority of type I diabetic families. Although environmental factors are clearly important in triggering the disease process in susceptible individuals, HLA genotyping of unaffected siblings can identify which siblings are at greater risk.…”

Section: Discussionmentioning

confidence: 96%

“…For example, some investigators favor a dominant inheritance, 5 whereas others argue that the results from family studies are compatible with an autosomal recessive pattern. 6 The Achilles' heel of these arguments is the relatively small number of families studied (usually [10][11][12][13][14][15][16][17][18][19][20] and, secondly, the absence of reliable information concerning the true prevalence of the disease.…”

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confidence: 99%

Type I (Insulin-dependent) Diabetic Multiplex Families: Mode of Genetic Transmission

Walker

Cudworth

1980

Diabetes

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SUMMARYHLA genotypes have been analyzed in 120 classic type I (insulin-dependent) diabetic sib pairs with an age of onset below 16 yr reported to the British Diabetic Association register (1972-78). By this age, siblings of diabetic children are 26 times more likely to develop type I diabetes than other children. There is a highly significant disturbance in the zygotic assortment of HLA haplotypes in these sib pairs, providing conclusive evidence for the existence of major susceptibility genes in the HLA complex.The present data exclude a simple dominant or recessive mode of inheritance. It is likely that both parents contribute to the susceptibility, indicating the presence of two HLA-linked genes (or clusters of genes in linkage disequilibrium) that influence the predisposition to the disease. There is no evidence that type I diabetic multiplex families have an increased HLA risk or increased predisposition to autoimmunity compared with families with one affected child. DIABE-TES 29:1036-1039, December 1980.

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“…previously called DR2 short, AZH, or FJO)II (1)(2)(3)(4)(5)(6)(7)(8). In contrast, an extremely decreased frequency is observed for the DRw15 specificity (a subdivision of DR2 previously called DR2 long)11 (1,9,10).…”

mentioning

confidence: 97%

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ABSTRACTSince HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of An increased frequency of some HLA-DR specificities has been reported among patients with insulin-dependent diabetes mellitus (IDDM): DR3, DR4, and, to a lesser extent, DR1, DRw13, and DRw16 (the last being a subdivision of DR2 previously called DR2 short, AZH, or FJO)II (1)(2)(3)(4)(5)(6)(7)(8). In contrast, an extremely decreased frequency is observed for the DRw15 specificity (a subdivision of DR2 previously called DR2 long)11 (1,9, 10).

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mentioning

confidence: 99%

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

Sterkers

Zeliszewski²,

Chaussée³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of An increased frequency of some HLA-DR specificities has been reported among patients with insulin-dependent diabetes mellitus (IDDM): DR3, DR4, and, to a lesser extent, DR1, DRw13, and DRw16 (the last being a subdivision of DR2 previously called DR2 short, AZH, or FJO)II (1)(2)(3)(4)(5)(6)(7)(8). In contrast, an extremely decreased frequency is observed for the DRw15 specificity (a subdivision of DR2 previously called DR2 long)11 (1,9, 10). Because of an aberrant expres-

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Type 1 diabetes and the HLA-D locus

Cited by 63 publications

References 5 publications

Diabetes in the parents of children with Type I diabetes

Diabetes in the parents of children with Type I diabetes

Type I (Insulin-dependent) Diabetic Multiplex Families: Mode of Genetic Transmission

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

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