title: Genetic variations in the mycophenolate mofetil target enzyme are associated with acute GVHD risk after related and unrelated hematopoietic cell transplantation.
abstract: Inosine monophosphate dehydrogenase (IMPDH) is the target enzyme of mycophenolate mofetil (MMF). Single nucleotide polymorphisms (SNPs) in the IMPDH1 gene are reportedly relevant to acute rejection in renal transplant patients receiving MMF. The objective of this study was to identify the impact of IMPDH1 gene polymorphisms on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Four IMPDH1 gene SNPs (IVS7 +125 G>A, IVS8-106 G>A, exon15 1572 G>A, and 5' flanking intron-exon region C>T) were analyzed in 240 consecutive pairs of transplant recipients and their donors. The presence of the IMPDH1 IVS8-106 G/G genotype in recipients was associated with a significantly higher incidence of acute graft-versus-host disease (aGVHD) than other genotypes, in both unrelated and sibling transplantation cohorts (unrelated cohort: 83.3% vs 63.9%, P = .048; sibling cohort: 47.6% vs 17.3%, P = .008). Multivariate analysis confirmed that recipients with the IVS8-106 G/G genotype were at significantly higher risk of developing aGVHD (relative risk [RR] = 2.018, 95% confidence interval [CI]: 1.354-3.009, P = .001) and grades II-IV aGVHD (RR = 2.232, 95% CI: 1.352-3.685, P = .002). There was no association among IVS7 +125, exon15 1572, and 5' flanking intron-exon region genotypes and the risk of aGVHD. These results represent the first report of an association between IMPDH1 gene polymorphisms and the risk of aGVHD in allo-HSCT.
authors: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang province, People's Republic of China.
authors: Weijie
authors: W
authors: Cao
authors: Haowen
authors: H
authors: Xiao
authors: Xiaoyu
authors: X
authors: Lai
authors: Yi
authors: Y
authors: Luo
authors: Jimin
authors: J
authors: Shi
authors: Yamin
authors: Y
authors: Tan
authors: Weiyan
authors: W
authors: Zheng
authors: Jingsong
authors: J
authors: He
authors: Wanzhuo
authors: W
authors: Xie
authors: Li
authors: L
authors: Li
authors: Xiujin
authors: X
authors: Ye
authors: Xiaohong
authors: X
authors: Yu
authors: Maofang
authors: M
authors: Lin
authors: Zhen
authors: Z
authors: Cai
authors: He
authors: H
authors: Huang
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D035781:Siblings; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; D009173:Mycophenolic Acid