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Fourlanos S _ et al_. (2008) The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes. _Diabetes Care_ 31: 1546–1549 The incidence
of childhood-onset type 1 diabetes mellitus (T1DM) has been increasing for decades. Fourlanos and colleagues investigated the contribution of environmental versus hereditary factors (in
particular the human leukocyte antigen [HLA] class II DRB1 genotype) to this rising incidence. The study included 462 Australian people of white origin, diagnosed with T1DM before age 18
years between 1950 and 2005. Decade of birth, age at diagnosis, and HLA-DRB1 genotype were determined in all participants. The mean age at diagnosis (8.5 ± 4.5 years) did not change over
decades. Changes were observed, however, in the frequency of the genotype conferring the highest risk, DR3,4, and of intermediate-risk genotypes DR4,X and DR3,X. The proportion of
participants carrying the DR3,4 allele was 79% in the group born between 1950 and 1969 and 28% among those born between 2000 and 2005 (_P_ <0.0001). The combined frequency of DR4,X and
DR3,X increased from 20% to 48% during the same period (_P_ = 0.0002). Moreover, in those carrying intermediate risk genotypes (DR4,4, DR3,3, DR4,X or DR3,X), age at diagnosis decreased over
decades. The frequency of the lowest-risk genotype, DRX,X was ≤3% in all cohorts. These data imply that the main reason for the rising incidence of T1DM is the increasing frequency of
intermediate-risk HLA-DRB1 genotypes, which have a greater penetrance in the 'diabetogenic' environment of our era than in previous decades. RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Contribution of genetic factors to type 1 diabetes has changed but not decreased. _Nat Rev Endocrinol_ 4, 587 (2008).
https://doi.org/10.1038/ncpendmet0959 Download citation * Issue Date: November 2008 * DOI: https://doi.org/10.1038/ncpendmet0959 SHARE THIS ARTICLE Anyone you share the following link with
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