We analyzed the CaN pathway gene variants previously associated with ex-vivo TAC PD in healthy volunteers (8) (i.e., PPIA rs8177826 and 6850; PPP3CA rs45441997; IL2RA rs10795791, 11594656, and 35285258), as well as 2 additional key genes of TAC pharmacodynamics (PPP3R1 rs4519508 andFKBP1A rs141252617).
In addition, 10 ng of genomic DNA were amplified by use of forward and reverse primers and then sequenced for the upstream 5'UTR region of PPIA and the 5'UTR regions of PPP3R1 and PPP3CA, to detect polymorphisms that could modulate DNA transcription or mRNA stability.
 Human genes: TNF[alpha], tumor necrosis factor alpha; PPIA, peptidylprolyl isomerase A; PPP3CA, protein phosphatase 3 catalytic subunit alpha; PPP3R1, protein phosphatase 3 regulatory subunit B, alpha; IL2RA, interleukin 2 receptor subunit alpha.
As shown, CIB4 has an interaction with protein phosphatase 3 catalytic subunit beta isozyme (PPP3CB), serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform (PPP3CC) and serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform (PPP3CA), that are three different isozymes of human PPP3C (22).
Alpha (PPP3CA), calcineurin A beta (PPP3CB) and calcineurin B (PPP3R1) are located on human chromosomes 4,10q21 [right arrow] q22 and 2p16 [right arrow] p15 respectively.
Your Input CSB4 calcium and Integrin-binding family member 4 (185 aa) Predicted Functional Partners: PPP3C8 protein phosphatase 3, catalytic subunit beta Isozyme (139 aa) PPP3CC serine/threonine-protein phosphatase 2B catalytic subunit gamma Isoform (512 aa) ENSBTAG00000019525 serine/threonine-protein phosphatase 2B catalytic subunit beta Isoform (369 aa) PPP3CA Serine/threonine-protein phosphatase 2B catalytic subunit alpha Isoform; Calcium- dependent, calmodulin-sti...
Panobinostat reduced MM cell proliferation by destroying protein phosphatase 3 catalytic subunit a (PPP3CA
), a catalytic subunit of calcineurin.
hydronephrosis Imipramine ADRA18, ADRA1D Renal nephritis Imipramine TP53, NOS1, CTNS, ALB, NFKB2, VDR, PDE4D, PPP3CA
, ACE Heart failure lmipramine EPO, NOS1, ATP1A3, CACNA1D, ACCN3, KCNG2, PDE4D, SLC9A1, TTN, ADRB3, KCNJ11, ADRA1D.
STRING analysis of this group of proteins showed a main interaction group among proteins WDR82, PPP1R2, PPP3CB, PPP3CA
, and EPS15 (Supp.
DNA from the 30 healthy volunteers of the main study was sequenced for the promoter region of PPIA [peptidylprolyl isomerase A (cyclophilin A)],  PPP3R1 (protein phosphatase 3, regulatory subunit B, [alpha]), PPP3CA (protein phosphatase 3, catalytic subunit, a isozyme), PPP3CB (protein phospha- 8 tase 3, catalytic subunit, [beta] isozyme), and FKBP1A (FK506 binding protein 1A, 12 kDa) to investigate polymorphisms that could modulate DNA transcription or mRNA stability (see online Supplemental Methods).
PPP3CA rs45441997 explained 23% of [IL2.sup.+][CD4.sup.+] [I.sub.max] variability (corrected P = 0.0280), and PPIA rs8177826 C>G explained 37% of NFAT1 [IC.sub.50] variability (corrected P = 0.0420).
PPP3CA rs45441997 (GCC)10/10 is a 5' untranslated region variation located in the promoter region of the catalytic subunit of calcineurin.