Abstract
Our previous results have suggested that genes outside the human leukocyte antigen (HLA) class II locus may affect the phenotype of type 2 diabetic patients from families with both type 1 and type 2 diabetes (mixed type 1/2). To study whether the TNF alpha gene could be such a modifying gene, we studied TNF alpha promoter polymorphisms (G-->A substitution at positions -308 and -238) in relation to HLA-DQB1 genotypes in type 2 patients from mixed type 1/2 families or common type 2 diabetes families as well as in patients with adult-onset type 1 diabetes and control subjects. The TNF alpha(308) AA/AG genotype frequency was increased in adult onset type 1 patients (55%, 69 of 126), but it was similar in type 2 patients from type 1/2 families (35%, 33/93) or common type 2 families (31%, 122 of 395), compared with controls (33%, 95/284; P < 0.0001 vs. type 1). The TNF alpha(308) A and DQB1*02 alleles were in linkage disequilibrium in type 1 patients (Ds = 0.81; P < 0.001 vs. Ds = 0.25 in controls) and type 2 patients from type 1/2 families (Ds = 0.59, P < 0.05 vs. controls) but not in common type 2 patients (Ds = 0.39). The polymorphism was associated with an insulin-deficient phenotype in the type 2 patients from type 1/2 families ...Continue Reading
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