OBJECTIVE: The minor allele of the nonsynonymous single nucleotide polymorphism (SNP) @entity68677 within the @entity5812 gene is positively associated with type 1 @entity6 and other @entity792 . Genetic and functional data underline its causal effect, but some studies suggest that this polymorphism does not entirely explain disease association of the @entity5812 region. The aim of this study was to evaluate type 1 @entity6 association within this gene in the Sardinian population. RESEARCH DESIGN AND METHODS: We resequenced the exons and potentially relevant portions of @entity5812 and detected 24 polymorphisms (23 SNPs and 1 @entity59231 [ @entity59231 ]), 8 of which were novel. A representative set of 14 SNPs and the @entity59231 were sequentially genotyped and assessed for disease association in 794 families, 490 sporadic @entity1 , and 721 matched control subjects. RESULTS: The @entity68677 variant, albeit rare in the general Sardinian population (allele frequency 0.014), was positively associated with type 1 @entity6 (P(one tail) = 3.7 x 10(-3)). In contrast, the background haplotype in which this mutation occurred was common (haplotype frequency 0.117) and neutrally associated with disease. We did not confirm disease associations reported in other populations for non @entity68677 variants ( @entity15335 , @entity43875 , and @entity43874 ), although they were present in appreciable frequencies in Sardinia. @entity425 associations with rare variants were detected in the Sardinian families but not confirmed in independent case-control sample sets and are most likely spurious. CONCLUSIONS: We provide further evidence that the @entity68677 polymorphism is primarily associated with type 1 @entity6 and exclude major contributions from other purportedly relevant variants within this gene.

Further evidence of a primary, causal association of the XXXX 620W variant with type 1 @entity6 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity68677 :: ('c|SUB|C|+1858|T', 'DNAMutation') :: ['+1858C>T'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity425 :: ('MESH:D018908', 'Disease') :: ['Additional weak disease'] @entity59231 :: ('MESH:C538284', 'Disease') :: ['deletion insertion polymorphism', 'DIP'] @entity43875 :: ('rs1310182', 'SNP') :: ['rs1310182'] @entity15335 :: ('rs2488457', 'SNP') :: ['rs2488457'] @entity5812 :: ('26191', 'Gene') :: ['PTPN22'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune diseases'] @entity43874 :: ('rs3811021', 'SNP') :: ['rs3811021']
@entity5812 :: (26191,Gene) :: ['PTPN22']
