PATERNALLY TRANSMITTED IDDM2 INFLUENCES DIABETES SUSCEPTIBILITY DESPITE BIALLELIC EXPRESSION OF THE INSULIN GENE IN HUMAN PANCREAS

Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM 2 influences IDDM susceptibility. We have analysed the Pst I+1127 poly morphism in 123 USA multiplex families and detected linkage only in ma le meioses using the affected sibpair analysis (P=0.009). Application of the transmission/disequilibrium test (TDT) found significantly incr eased transmission of the IDDM-associated (TDT) found significantly in creased transmission of the IDDM-associated INS allele from fathers he terozygous for INS to their diabetic offspring (P=0.00002), but the tr ansmission from heterozygous mothers was not significantly different f rom random expectation. In non-diabetic families, the transmission fro m parents heterozygous for INS was not significantly different from ra ndom expectation in either paternal or maternal meioses. Maternal impr inting of the INS gene in pancreatic islets was originally considered the most favorable explanation for the observed gender-related differe nce. However, our study has demonstrated biallelic expression of INS i n pancreatic tissues from human fetuses and thus suggests that INS is probably not imprinted in the pancreatic islets. (C) 1996 Academic Pre ss Limited