PMID- 18487476 OWN - NLM STAT- MEDLINE DCOM- 20080820 LR - 20221207 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 31 IP - 8 DP - 2008 Aug TI - The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes. PG - 1546-9 LID - 10.2337/dc08-0239 [doi] AB - OBJECTIVE: The rising incidence of type 1 diabetes has been attributed to environment, implying a lesser role for genetic susceptibility. However, the rise could be accounted for by either more cases with classic high-risk genes or by cases with other risk genes. Separately, for any degree of genetic susceptibility, age at presentation may decrease in a permissive environment. To examine these possibilities, human leukocyte antigen (HLA) class II DRB1 genes known to confer risk for type 1 diabetes were analyzed in relation to year of birth and age at diagnosis over the last five decades. RESEARCH DESIGN AND METHODS: Caucasoid subjects (n = 462) diagnosed with type 1 diabetes before age 18 between 1950 and 2005 were DRB1 genotyped. RESULTS: Mean +/- SD age at diagnosis, 8.5 +/- 4.5 years, did not differ across decades. Recent diagnosis was associated with a lower proportion but unchanged incidence of the highest-risk DRB1 genotype DR3,4 (2000-2005, 28% vs. 1950-1969, 79%; P < 0.0001) and a higher proportion of lower-risk genotypes DR4,X and DR3,X (2000-2005, 48% vs. 1950-1969, 20%; P = 0.0002). The frequency of the DRX,X genotype was low (