Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset

HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellit us were analysed in population-based Swedish patients and controls aged 0-3 4 years. The age dependence of HLA-associated relative risks was assessed b y likelihood ratio tests of regression parameters in separate logistic regr ession models for each HLA category. The analyses demonstrated an attenuati on with increasing age at onset in the relative risk for the positively ass ociated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and t he negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P=0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, b ut this increased to 1.1 at age 35 years. Relative risks for individuals wi th DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ hapl otype other than 2, 8 or 6.2, were not significantly age-dependent. An expl oratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that th e risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 hapl otype is at age 18 years. There was also weak evidence that the risk for DQ B1*0303-A1*0301 (DQ9), which has a positive association in the Japanese pop ulation, may decrease with age. We speculate that HLA-DQ alleles have a sig nificant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.