ABCMdb

PMID: 18239147

Burke MA, Mutharasan RK, Ardehali H
The sulfonylurea receptor, an atypical ATP-binding cassette protein, and its regulation of the KATP channel.
Circ Res. 2008 Feb 1;102(2):164-76., [PubMed]

Sentences

No. Mutations Sentence Comment

111 ABCC8 p.Ala1369Ser However, there is significant linkage disequilibrium between the KCNJ11 E23K polymorphism and a common polymorphism in ABCC8, A1369S.99 In fact, these 2 polymorphisms are almost always found together and seem to be protective of progression to diabetes in patients enrolled in the Diabetes Prevention Program. Login to comment 177 ABCC9 p.Val734Ile However, a rare mutation found in an Italian population encoding for a Val734Ile mutation in ABCC9 has been associated with a 6.4-fold increased risk of early myocardial infarction (defined as myocardial infarction before 60 years of age) compared with control patients.140 At present, the pathophysiological mechanism behind this increased risk is not known, but given the excessive vasospasm noted in the SUR2 KO, the authors posit that this mutation may increase the incidence of vasospasm, resulting in myocardial infarction. Login to comment 178 ABCC9 p.Thr1547Ile Another ABCC9 mutation in SUR2A has been identified recently in a patient with adrenergic-inducible atrial fibrillation.141 This mutation, T1547I, occurs at a highly conserved residue in the unique C-terminal 42-aa domain of SUR2A. Login to comment 179 ABCC9 p.Thr1547Ile As previously stated, this domain constitutes the only difference between SUR2A and SUR2B and is thought to play a major role in the differential gating exhibited by these 2 isoforms.113 This residue is predicted to be in close proximity to the Walker A motif of NBD2, and the T1547I mutation alters the normal hydrogen bonding that stabilizes this motif.141 This mutant SUR2A, coexpressed with Kir6.2, showed reduced responsiveness to ADP, while retaining the normal inhibitory effects of ATP, thus resulting in decreased channel gating.141 Experimental evidence also supports a possible role for SUR2A in ischemic heart disease. Login to comment