Tags

Type your tag names separated by a space and hit enter

Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country.

Abstract

OBJECTIVE

To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of beta-cell autoimmunity among three geographical regions in Finland.

RESEARCH DESIGN AND METHODS

The series comprised 4,642 children with increased HLA-DQB1-defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.5%) in Oulu, and 1,203 (25.9%) in Tampere. These children were examined frequently for the emergence of signs of beta-cell autoimmunity, for the primary screening of which islet cell antibodies (ICA) were used. If the child developed ICA, all samples were also analyzed for insulin autoantibodies (IAA), GAD65 antibodies (GADA), and antibodies to the IA-2 molecule (IA-2A).

RESULTS

The high- and moderate-risk genotypes were unevenly distributed among the three areas (P<0.001); the high-risk genotype was less frequent in the Oulu region (20.4%) than in the Turku (28.4%; P<0.001) or Tampere regions (27.2%; P<0.001). This genotype was associated with an increased frequency of ICA seroconversion relative to the moderate risk genotypes (hazard ratio 1.89, 95% CI 1.36-2.62). Seroconversions to ICA positivity occurred less commonly in Tampere than in Turku (0.47, 0.28-0.75), whereas the seroconversion rate in Oulu did not differ from that in Turku (0.72, 0.51-1.03). The Tampere-Turku difference persisted after adjustment for risk genotypes, sex, and time of birth (before January 1998 versus later). Seroconversion for at least one additional autoantibody was also less frequent in Tampere than in Turku (0.39, 0.16-0.82).

CONCLUSIONS

These data show that in Finland, the country with the highest incidence of type 1 diabetes in the world, both the frequency of the high-risk HLA-DQB1 genotype and the risk of seroconversion to autoantibody positivity show geographical variation. The difference in seroconversion rate could not be explained by the difference in HLA-DQB1-defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Juvenile Diabetes Research Foundation Center for the Prevention of Type 1 Diabetes in Finland, Tampere, Finland.

    , , , , , ,

    Source

    Diabetes care 27:3 2004 Mar pg 676-81

    MeSH

    Autoantibodies
    Child
    Child, Preschool
    Diabetes Mellitus, Type 1
    Finland
    Follow-Up Studies
    Genetic Variation
    Genotype
    Geography
    HLA-DQ Antigens
    HLA-DQ beta-Chains
    Humans
    Incidence
    Infant
    Islets of Langerhans
    Proportional Hazards Models
    Risk Assessment
    Time Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    14988284

    Citation

    Kukko, Marika, et al. "Geographical Variation in Risk HLA-DQB1 Genotypes for Type 1 Diabetes and Signs of Beta-cell Autoimmunity in a High-incidence Country." Diabetes Care, vol. 27, no. 3, 2004, pp. 676-81.
    Kukko M, Virtanen SM, Toivonen A, et al. Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country. Diabetes Care. 2004;27(3):676-81.
    Kukko, M., Virtanen, S. M., Toivonen, A., Simell, S., Korhonen, S., Ilonen, J., ... Knip, M. (2004). Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country. Diabetes Care, 27(3), pp. 676-81.
    Kukko M, et al. Geographical Variation in Risk HLA-DQB1 Genotypes for Type 1 Diabetes and Signs of Beta-cell Autoimmunity in a High-incidence Country. Diabetes Care. 2004;27(3):676-81. PubMed PMID: 14988284.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country. AU - Kukko,Marika, AU - Virtanen,Suvi M, AU - Toivonen,Anna, AU - Simell,Satu, AU - Korhonen,Sari, AU - Ilonen,Jorma, AU - Simel,Olli, AU - Knip,Mikael, PY - 2004/2/28/pubmed PY - 2004/9/24/medline PY - 2004/2/28/entrez SP - 676 EP - 81 JF - Diabetes care JO - Diabetes Care VL - 27 IS - 3 N2 - OBJECTIVE: To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of beta-cell autoimmunity among three geographical regions in Finland. RESEARCH DESIGN AND METHODS: The series comprised 4,642 children with increased HLA-DQB1-defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.5%) in Oulu, and 1,203 (25.9%) in Tampere. These children were examined frequently for the emergence of signs of beta-cell autoimmunity, for the primary screening of which islet cell antibodies (ICA) were used. If the child developed ICA, all samples were also analyzed for insulin autoantibodies (IAA), GAD65 antibodies (GADA), and antibodies to the IA-2 molecule (IA-2A). RESULTS: The high- and moderate-risk genotypes were unevenly distributed among the three areas (P<0.001); the high-risk genotype was less frequent in the Oulu region (20.4%) than in the Turku (28.4%; P<0.001) or Tampere regions (27.2%; P<0.001). This genotype was associated with an increased frequency of ICA seroconversion relative to the moderate risk genotypes (hazard ratio 1.89, 95% CI 1.36-2.62). Seroconversions to ICA positivity occurred less commonly in Tampere than in Turku (0.47, 0.28-0.75), whereas the seroconversion rate in Oulu did not differ from that in Turku (0.72, 0.51-1.03). The Tampere-Turku difference persisted after adjustment for risk genotypes, sex, and time of birth (before January 1998 versus later). Seroconversion for at least one additional autoantibody was also less frequent in Tampere than in Turku (0.39, 0.16-0.82). CONCLUSIONS: These data show that in Finland, the country with the highest incidence of type 1 diabetes in the world, both the frequency of the high-risk HLA-DQB1 genotype and the risk of seroconversion to autoantibody positivity show geographical variation. The difference in seroconversion rate could not be explained by the difference in HLA-DQB1-defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied. SN - 0149-5992 UR - https://www.unboundmedicine.com/medline/citation/14988284/Geographical_variation_in_risk_HLA_DQB1_genotypes_for_type_1_diabetes_and_signs_of_beta_cell_autoimmunity_in_a_high_incidence_country_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=14988284 DB - PRIME DP - Unbound Medicine ER -