Geographical Variation in Risk HLA-DQB1 Genotypes for Type 1 Diabetes and Signs of β-Cell Autoimmunity in a High-Incidence Country

Kukko, Marika; Virtanen, Suvi M.; Toivonen, Anna; Simell, Satu; Korhonen, Sari; Ilonen, Jorma; Simel, Olli; Knip, Mikael
March 2004
Diabetes Care;Mar2004, Vol. 27 Issue 3, p676
Academic Journal
To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of β-cell autoimmunity among three geographical regions in Finland. 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% C1 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). 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-DQB l 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-DQBl-defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied.


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