OBJECTIVES: @entity8265 autoantibodies (tTGAs) represent the first evidence of @entity1593 ( @entity1593 ) development. Associations of @entity8167 *05:01- @entity3098 *02:01 (i.e., @entity4106 -DQ2) and, to a lesser extent, @entity4107 -DQA1*03:01- @entity3098 *03:02 (i.e., @entity4107 -DQ8) with the risk of @entity1593 differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human @entity4107 for their contribution to developing tTGAs. METHODS: The Environmental Determinants of @entity6 in the Young (TEDDY) study enrolled 8,676 @entity1 at an increased HLA-DR-DQ risk for type 1 @entity6 and @entity1593 into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried @entity4106 -DQ2/ @entity4106 -DQ2, 39% (n=3,359) carried @entity4106 -DQ2/ @entity4107 -DQ8, 20% (n=1701) carried @entity4107 -DQ8/ @entity4107 -DQ8, and 17% (n=1,493) carried @entity4107 -DQ8/DQ4. Within TEDDY, a nested case-control design of 248 @entity1 with @entity792 ( @entity792 ) and 248 matched control @entity1 were genotyped for @entity1530 , - @entity4107 , -DPA1, and - @entity3099 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. @entity792 was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. RESULTS: After adjustment for @entity4106 -DQ2 and restriction to @entity4365 ( @entity4365 ) >= 5%, @entity3099 *04:01 was inversely associated with @entity792 by conditional logistic regression ( @entity4365 =44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to @entity792 and @entity3099 *04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). CONCLUSIONS: @entity3099 *04:01 may reduce the risk of tTGAs, an early marker of @entity1593 , among @entity4106 -DQ2 @entity1 , confirming that additional variants in the HLA region influence the risk for @entity792 .

XXXX *04:01 Protects Genetically Susceptible @entity1 from @entity1593 Autoimmunity in the TEDDY Study.

@entity1 :: ('9606', 'Species') :: ['children', 'infants'] @entity3099 :: ('3115', 'Gene') :: ['HLA-DPB1', 'DPB1'] @entity1593 :: ('MESH:D002446', 'Disease') :: ['celiac disease', 'CD'] @entity6 :: ('MESH:D003920', 'Disease') :: ['Diabetes', 'diabetes'] @entity4106 :: ('8718', 'Gene') :: ['DR3'] @entity3098 :: ('3119', 'Gene') :: ['DQB1'] @entity1530 :: ('3106', 'Gene') :: ['HLA-B, -DRB3'] @entity8265 :: ('7052', 'Gene') :: ['Tissue transglutaminase'] @entity4365 :: ('MESH:C565121', 'Disease') :: ['AF', 'allele frequency'] @entity8167 :: ('3117', 'Gene') :: ['HLA-DR3-DQA1'] @entity792 :: ('MESH:D001327', 'Disease') :: ['CD autoimmunity', 'CDA'] @entity4107 :: ('3126', 'Gene') :: ['DRB4', 'DR4', 'leukocyte antigen (HLA) factors other than DR3-DQ2']
@entity3099 :: (3115,Gene) :: ['HLA-DPB1']
