Calcineurin a calmodulin-dependent phosphatase plays a critical role in cal
cium-dependent activation of T-lymphocytes and is the major target for the
inhibitory actions of the immunosuppressive drugs Tacrolimus (FK506) and Cy
closporin A (CsA). Calcineurin is a dimeric protein consisting of distinct
A (catalytic) and B (regulatory) subunits. In humans two separate genes, CN
A1 and CNA2, encode the calcineurin A (CNA) subunit. The region of CNA that
interacts with Calcineurin B, calmodulin, and inumunosuppressive drugs bou
nd to their receptors - the immunophilins - has been identified to amino ac
ids 281-414 (Greengard P, Alien PB ,Nairin AC. Beyond the dopamine receptor
: the DARPP-32/protein phosphatase-l cascade. Neuron 1999;23:435). Our work
ing hypothesis was that the differences in patient response to calcineurin
inhibitors could be a consequence of inherited variations within their CNA
genes. Single-strand conformational polymorphism (SSCP) analysis of cDNAs d
erived from the coding region for amino acids 281-414 of CNA1 and CNA2 in 3
2 healthy Caucasians did not detect polymorphic variations within these gen
es. These results suggest that this region is highly conserved and cannot a
ccount for individual variation in response of patients to FK506 and CsA tr
eatment. (C) 2000 Elsevier Science B.V. All rights reserved.