ABCMdb

PMID: 20099993

Bai JP, Lesko LJ, Burckart GJ
Understanding the genetic basis for adverse drug effects: the calcineurin inhibitors.
Pharmacotherapy. 2010 Feb;30(2):195-209., [PubMed]

Sentences

No. Mutations Sentence Comment

65 ABCC8 p.Ala1166Cys (continued) Risk Factors ACE (rs4340) D/D (+) (RR 5.28, 95% CI 2.48-11.24, p<0.0001) AGT (rs5051) (-), AGTR1 (rs5186) (-) TGF-beta protein expression significantly higher in those with acute cyclosporine toxicity than those with acute rejection or chronic allograft nephropathy (p<0.05) Tissue factor expression (+) (p=0.0026 for 18 transplant recipients with cyclosporine nephrotoxicity vs 6 patients with normal kidneys) -657 4G allele (rs1799889) (+) (p=0.0189) (exponential coefficient of survival regression 3.35, 95% CI 1.22-9.22) ACE I/D (rs4340) (-) AGT M235T T allele (rs 699) (+) (OR 1.33, 95% CI 1.04-1.70, p=0.02) AGTR1 C allele and CC (rs5186) (+) C allele (OR 1.87, 95% CI 1.49-2.35, p<0.0001) ACE (rs4340) (-) D allele (OR 0.92, 95% CI 0.70-1.20, p=0.59) ACE D allele (rs4340) (+) (OR 1.34, 95% CI 1.07-1.69, p=0.01) AGT M235T (rs699) (+) (OR 0.74, 95% CI 0.59-0.94, p=0.01) AGTR1 A1166C (rs388915) (-) TNF -308 AA, AG, GG (rs1088629) (-) TGFB1 (codon 10) TT (rs1800470) (+) (OR 5.31, 95% CI 3.77-7.02, p<0.001) IL10 (-1082) GG (rs1800896) (+) (OR 2.35, 95% CI 1.67-3.15, p<0.01) Hyperuricemia: TGFB1 G/G (rs1800471) (+) (p=0.0013) TGFB1 (codon 10) (rs1800470) (-) IL10 AG (-1082) (rs1800896) (+) (p=0.0022) Type 2 or steroid-induced diabetes mellitus: IFNG (+874 AA) (rs2430561) (+) (p=0.0127) IL10 (-1082 A/G) (rs1800896) (-) IL1RN 2-repeat allele (VNTR 2 copies ) (+) (OR 1.46, 95% CI 1.19-1.78, p<0.01) IL1B (-511) (rs16944) (-) tacrolimus group had decreased insulin secretion.27 The exact mechanism of calcineurin inhibitor-induced toxicity to the beta cell is unknown. Login to comment 101 ABCC8 p.Ala1369Ser ABCC8 p.Ala1369Ser Blockade of the mutant KATP channel by sulfonylurea provides the genetic basis for understanding the efficacy of sulfonylurea agents in treating neonatal diabetes.51 In a diabetes prevention randomized clinical trial of 3548 patients at 27 centers, both KCNJ11 E23K (rs5219) and ABCC8 A1369S (rs757110) were statistically significantly associated with impaired glucose tolerance at baseline.52 The alanine carrier of ABCC8 A1369S seemed to carry the lysine allele of KCNJ11 E23K as well. Login to comment 102 ABCC8 p.Ala1369Ser Of interest, this study revealed that the lysine allele (or the alanine allele of ABCC8 A1369S) seemed to protect the development of diabetes at the year-1 assessment (p<0.01). Login to comment