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Predisposition to type 1 diabetes and juvenile obesity is influenced by the susceptibility locus IDDM2 that includes the insulin gene (INS). Although the risk conferred by IDDM2 has been attributed to a minisatellite upstream of INS, intragenic variants have not been ruled out. We examined whether INS polymorphisms affect pre-mRNA splicing and proinsulin secretion using minigene reporter assays. We show that IVS1-6A/T (؊23HphI؉/؊) is a key INS variant that influences alternative splicing ofdoi:10.2337/diabetes.55.01.06.db05-0773 pmid:16380501 fatcat:bgw2tcklcrbfnfxyyzvm6qo2km