Islet cell antibody-positive relatives with human leukocyte antigen DQA1*0102, DQB1*0602: identification by the Diabetes Prevention Trial-type 1.

The presence of human leukocyte antigen (HLA) haplotype DQA1*0102, DQB1*0602 is associated with protection from type 1 diabetes. The Diabetes Prevention Trial-type 1 has identified 100 islet cell antibody (ICA)-positive relatives with this protective haplotype, far exceeding the number of such subjects reported in other studies worldwide. Comparisons between ICA+ relatives with and without DQB1*0602 demonstrated no differences in gender or age; however, among racial groups, African-American ICA+ relatives were more likely to carry this haplotype than others. The ICA+ DQB1*0602 individuals were less likely to have additional risk factors for diabetes [insulin autoantibody (IAA) positive or low first phase insulin release (FPIR)] than ICA+ relatives without DQB1*0602. However, 29% of the ICA+ DQB1*0602 relatives did have IAA or low FPIR. Although half of the ICA+ DQB1*0602 relatives had a high risk second haplotype, this was not associated with the additional risk factors for diabetes. Hispanic ICA+ individuals with DQB1*0602 were more likely to be IAA positive or to have low FPIR than other racial groups. In conclusion, the presence of ICA in the relatives described here suggests that whatever the mechanism that protects DQB1*0602 individuals from diabetes, it is likely to occur after the diabetes disease process has begun. In addition, there may be different effects of DQB1*0602 between ethnic groups.

[1]  H. Erlich,et al.  Sequence analysis of the diabetes-protective human leukocyte antigen-DQB1*0602 allele in unaffected, islet cell antibody-positive first degree relatives and in rare patients with type 1 diabetes. , 1999, The Journal of clinical endocrinology and metabolism.

[2]  N. Breslow,et al.  Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset: Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset , 1999 .

[3]  J. Kira,et al.  Peptide-based molecular analyses of HLA class II-associated susceptibility to autoimmune diseases. , 1998, International reviews of immunology.

[4]  William W Kwok,et al.  Molecular Basis for HLA-DQ Associations With IDDM , 1998, Diabetes.

[5]  L. Kuller,et al.  Was There an Epidemic of Diabetes in Nonwhite Adolescents in Allegheny County, Pennsylvania? , 1998, Diabetes Care.

[6]  J. Cassiman,et al.  Reevaluation of the importance of polymorphic HLA class II alleles and amino acids in the susceptibility of individuals of different populations to type I diabetes. , 1998, American journal of medical genetics.

[7]  M. Hoover,et al.  Molecular Modelling of HLA‐DQ Suggests a Mechanism of Resistance in Type 1 Diabetes , 1997, Scandinavian journal of immunology.

[8]  P. Bingley Interactions of age, islet cell antibodies, insulin autoantibodies, and first-phase insulin response in predicting risk of progression to IDDM in ICA+ relatives: the ICARUS data set. Islet Cell Antibody Register Users Study. , 1996 .

[9]  P. Bingley Interactions of Age, Islet Cell Antibodies, Insulin Autoantibodies, and First-Phase Insulin Response in Predicting Risk of Progression to IDDM in ICA+ Relatives: The ICARUS Data Set , 1996, Diabetes.

[10]  M. Rewers,et al.  Antiislet autoantibodies usually develop sequentially rather than simultaneously. , 1996, The Journal of clinical endocrinology and metabolism.

[11]  J. Ilonen,et al.  Effect of polymorphism in the insulin gene region on IDDM susceptibility and insulin secretion ** , 1996, European journal of clinical investigation.

[12]  Å. Lernmark,et al.  Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus. The Swedish Childhood Diabetes Study Group and The Diabetes Incidence in Sweden Study (DISS) Group. , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[13]  G. Eisenbarth,et al.  Limited loss of tolerance to islet autoantigens in ICA+ first degree relatives of patients with type I diabetes expressing the HLA dqb1*0602 allele. , 1996, Journal of autoimmunity.

[14]  W. Klitz,et al.  Association of HLA-DPB1*0301 With IDDM in Mexican-Americans , 1996, Diabetes.

[15]  J. She,et al.  HLA-encoded susceptibility to insulin-dependent diabetes mellitus is determined by DR and DQ genes as well as their linkage disequilibria in a Chinese population. , 1995, Human immunology.

[16]  J. Ilonen,et al.  Human Leukocyte Antigen Identity and DQ Risk Alleles in Autoantibody-Positive Siblings of Children With IDDM are Associated With Reduced Early Insulin Response , 1995, Diabetes.

[17]  H. Erlich,et al.  HLA-DQB1*0602 Is Associated With Dominant Protection From Diabetes Even Among Islet Cell Antibody–Positive First-Degree Relatives of Patients with IDDM , 1995, Diabetes.

[18]  Z. Layrisse,et al.  HLA-DP and susceptibility to insulin-dependent diabetes mellitus in an ethnically mixed population. Associations with other HLA-alleles. , 1995, Journal of autoimmunity.

[19]  M. Knip,et al.  Effect of genetic risk load defined by HLA‐DQB1 polymorphism on clinical characteristics of ID DM in children , 1995, European journal of clinical investigation.

[20]  N. Maclaren,et al.  High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them. , 1994, Journal of autoimmunity.

[21]  Z. Layrisse,et al.  HLA‐DQA1 AND DQB 1 ALLELE AND GENOTYPE CONTRIBUTION TO IDDM SUSCEPTIBILITY IN AN ETHNICALLY MIXED POPULATION , 1994, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.

[22]  L. Chuang Immunogenetics and IDDM , 1994 .

[23]  A. Amoroso,et al.  Human Leukocyte Antigen Class II Polymorphisms and Genetic Susceptibility of IDDM in Egyptian Children , 1994, Diabetes Care.

[24]  Y. Kanazawa,et al.  Genetic markers for insulin-dependent diabetes mellitus in Japanese. , 1994, Diabetes research and clinical practice.

[25]  J. Todd,et al.  Ethnic Differences in Human Leukocyte Antigen Markers of Susceptibility to IDDM , 1994, Diabetes Care.

[26]  J. Rotter,et al.  Analysis of HLA-DQA1 and -DQB1 genes in Mexican Americans with insulin-dependent diabetes mellitus. , 1993, Tissue antigens.

[27]  P. Bingley,et al.  Comparison of Bolus and Infusion Protocols for Determining Acute Insulin Response to Intravenous Glucose in Normal Humans , 1993, Diabetes Care.

[28]  Henry A. Erlich,et al.  HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families , 1993, Nature Genetics.

[29]  P. Raskin,et al.  Genes for insulin-dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) of African-Americans. , 1993, Tissue antigens.

[30]  C. Boitard,et al.  Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus. , 1992, The Journal of clinical investigation.

[31]  H. Erlich,et al.  Implication of Specific DQB1 Alleles in Genetic Susceptibility and Resistance by Identification of IDDM Siblings With Novel HLA-DQB1 Allele and Unusual DR2 and DR1 Haplotypes , 1991, Diabetes.

[32]  J. D. Capra,et al.  Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. , 1990, The New England journal of medicine.

[33]  H A Erlich,et al.  Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[34]  W. Hagopian,et al.  Genetic and immunological markers of insulin dependent diabetes in Black Americans. , 1995, Autoimmunity.

[35]  J. Ilonen,et al.  Multi-locus analysis of HLA class II genes in DR2-positive IDDM haplotypes in Finland. The "Childhood Diabetes in Finland" (DiMe) Study Group. , 1994, Tissue antigens.