The possibility of a significant discordance in the correlation between genotype and phenotype needs to be taken into account when ABCC8 mutation dependent diabetes occurs within the same family.
Patients with dominant ABCC8 gene mutations are prone to DM in adulthood, but Sirolimus therapy might increase the risk of developing diabetes at an early age, as this case illustrates.
A total of 40 individuals with diabetes (1.8% of early onset sub-group and 0.6% of adult onset sub-group) were carriers of known pathogenic missense variants in the GCK, HNF1A, HNF4A, ABCC8, and INS genes.
Furthermore, the sulfonylurea receptor 1 (SUR1) S1369Adiabetes risk variant increases MgATPase activity, but the molecular mechanisms remain to be determined.
We report a case of a 6-week-old infant with diabetes mellitus based on a genetic defect in the sulfonylurea receptor 1 (SUR1), an ATP-sensitive potassium (KATP) channel protein.
Activating mutations in the ABCC8 gene encoding the KATP channel subunit SUR1 cause β-cell dysfunction with non-autoimmune diabetes mellitus in neonates or infants.
STZ treatment also suppressed expression of a wide range of genes linked with key β-cell functions or diabetes development, such as G6pc2, Slc2a2 (Glut2), Slc30a8, Neurod1, Ucn3, Gad1, Isl1, Foxa2, Vdr, Pdx1, Fkbp1b and Abcc8, suggesting global β-cell defects in STZ-treated islets.
The KCNJ11 and ABCC8 genes were sequenced in 115 infants with permanent diabetes diagnosed between 6 and 12 months and in 405 patients presenting before 6 months.
Thus, MRP8/14 likely plays a role in exaggerated ISR in diabetes mellitus, and MRP8 inhibition may be useful in improving outcome after stent placement in diabetes mellitus.
Studies have suggested that the VDR, PPARG, HNF1A, and adenosine 5'-triphosphate-binding cassette ABCC8 (which encodes the sulfonylurea receptor) genes are associated with calcineurin inhibitor-induced diabetes.
Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood.
Multiple mutations in Kir6.x and SUR genes have implicated K(ATP) channels in various diseases ranging from diabetes and hyperinsulinism to cardiac arrhythmias and cardiovascular disease.
The meta-analysis of East Asian populations also showed a strong significant association of the K allele with diabetes (OR=1.15, P=3 x 10(-9)), whereas the exon16-3t/c variant (rs1799854) in ABCC8 showed no significant association.