In Finland insulin gene region encoded susceptibility to IDDM exerts maximum effect when there is low HLA-DR associated risk View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1995-10

AUTHORS

K. A. Metcalfe, G. A. Hitman, M. J. Fennessy, M. I. McCarthy, J. Tuomilehto, E. Tuomilehto-Wolf, The DiMe (Childhood Diabetes in Finland) Study Group

ABSTRACT

An association between insulin-dependent diabetes mellitus (IDDM) and polymorphisms of the insulin gene on chromosome 11p15 (INS) is a consistent finding in Europid populations. While one study suggested that the INS association is restricted to HLA-DR4-positive individuals, studies in other Europid populations have shown the disease-associated INS genotype to confer susceptibility independently of HLA-DR. We have investigated the role of INS in susceptibility to IDDM in Finland, which has the highest incidence of diabetes mellitus in the world, at two polymorphic restriction sites, 5′ and 3′ to the insulin gene. From the DiMe (Childhood Diabetes in Finland) Study we studied 154 diabetic children without regard to HLA-DR type; 108 DR4 positive/non-DR3 diabetic children; 39 DR3 positive/non-DR4 diabetic children; 30 DR4/DR3 positive diabetic children; 31 non-DR4/non-DR3 diabetic children; 96 matched DiMe control subjects and 86 other healthy, non-diabetic Finnish control subjects. We found an overall association between IDDM and INS in the high-risk Finnish population only with the 5′ polymorphism and identified an INS haplotype negatively associated with IDDM in Finland. However, among diabetic subjects with a reduced HLA-associated susceptibility (non-DR4/non-DR3) both 3′ and 5′ INS loci showed an association with IDDM (p values 0.02 and 0.0002, respectively). Thus, in the Finnish population insulin gene-encoded susceptibility to IDDM exerts a maximum effect in those with reduced HLA-associated risk. More... »

PAGES

1223-1229

References to SciGraph publications

  • 1992-11. Insulin gene region–encoded susceptibility to type 1 diabetes is not restricted to HLA–DR4–positive individuals in NATURE GENETICS
  • 1994-09. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome llq in NATURE
  • 1992-01. Epidemiology of childhood diabetes mellitus in Finland — background of a nationwide study of Type 1 (insulin-dependent) diabetes mellitus in DIABETOLOGIA
  • 1987-10. HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus in NATURE
  • 1980-03. Sequence of the human insulin gene in NATURE
  • 1980-01. Type 1 diabetes and the HLA-D locus in DIABETOLOGIA
  • 1985-04. Type 1 (insulin-dependent) diabetes and a highly variable locus close to the insulin gene on chromosome 11 in DIABETOLOGIA
  • 1991-11. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility in NATURE
  • 1993-07. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR in NATURE GENETICS
  • 1983-04. The genetic susceptibility to type 1 (insulin-dependent) diabetes: Analysis of the HLA-DR association in DIABETOLOGIA
  • 1986-07. New HLA DNA polymorphisms associated with autoimmune diseases in NATURE
  • 1992-03. HLA haplotypes in Type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus in DIABETOLOGIA
  • 1994-09. A genome-wide search for human type 1 diabetes susceptibility genes in NATURE
  • 1995-03. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus in NATURE GENETICS
  • 1995-03. The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription in NATURE GENETICS
  • 1989-01. The genetic predisposition to fibrocalculous pancreatic diabetes in DIABETOLOGIA
  • 1994-08. IDDM susceptibility associated with polymorphisms in the insulin gene region A study of blacks, Caucasians and orientals in DIABETOLOGIA
  • 1994-10. A locus on chromosome 15q26 (IDDM3) produces susceptibility to insulin-dependent diabetes mellitus in NATURE GENETICS
  • 1985-12. Restriction fragment length polymorphism of the insulin gene region in Japanese diabetic and non-diabetic subjects in DIABETOLOGIA
  • 1994-09. A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population in DIABETOLOGIA
  • 1995-01. Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31–q33 in NATURE GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf00422373

    DOI

    http://dx.doi.org/10.1007/bf00422373

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053011169

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/8690176


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    47 schema:description An association between insulin-dependent diabetes mellitus (IDDM) and polymorphisms of the insulin gene on chromosome 11p15 (INS) is a consistent finding in Europid populations. While one study suggested that the INS association is restricted to HLA-DR4-positive individuals, studies in other Europid populations have shown the disease-associated INS genotype to confer susceptibility independently of HLA-DR. We have investigated the role of INS in susceptibility to IDDM in Finland, which has the highest incidence of diabetes mellitus in the world, at two polymorphic restriction sites, 5′ and 3′ to the insulin gene. From the DiMe (Childhood Diabetes in Finland) Study we studied 154 diabetic children without regard to HLA-DR type; 108 DR4 positive/non-DR3 diabetic children; 39 DR3 positive/non-DR4 diabetic children; 30 DR4/DR3 positive diabetic children; 31 non-DR4/non-DR3 diabetic children; 96 matched DiMe control subjects and 86 other healthy, non-diabetic Finnish control subjects. We found an overall association between IDDM and INS in the high-risk Finnish population only with the 5′ polymorphism and identified an INS haplotype negatively associated with IDDM in Finland. However, among diabetic subjects with a reduced HLA-associated susceptibility (non-DR4/non-DR3) both 3′ and 5′ INS loci showed an association with IDDM (p values 0.02 and 0.0002, respectively). Thus, in the Finnish population insulin gene-encoded susceptibility to IDDM exerts a maximum effect in those with reduced HLA-associated risk.
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