title: Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort.
abstract: There have been numerous reports proposing a statistically significant association between a genetic variant, usually in the form of a single nucleotide polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional publications reporting a lack of association with AR when a different cohort of recipients was analyzed for the same SNP. The objective of this report was to attempt replication of these published finding in our own kidney allograft recipient cohort. We analyzed 23 genetic variants, previously reported to have a significant association with AR, using a cohort of 969 clinically well-defined kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the coagulation factor V gene, showed a significant association with a P-value of 0.011 in a race-adjusted analysis and a P-value of 0.0003 in multiple variable analysis. An additional SNP, rs11706052 in IMPDH2, gave a modest P-value of 0.044 using multiple variable analysis, which is not significant when multiple testing is taken into consideration. Our results suggest that careful validation of previously reported associations with AR is necessary, and different strategies other than candidate gene studies can help to identify causative genetic variants associated with AR.
authors.affiliation: College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. oetti001@umn.edu
authors.forename: William S
authors.initials: WS
authors.lastname: Oetting
authors.forename: David P
authors.initials: DP
authors.lastname: Schladt
authors.forename: Robert E
authors.initials: RE
authors.lastname: Leduc
authors.forename: Pamala A
authors.initials: PA
authors.lastname: Jacobson
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Matas
authors.forename: Ajay
authors.initials: A
authors.lastname: Israni
mesh_terms: D000208:Acute Disease; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D006084:Graft Rejection / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects*; D016035:Pancreas Transplantation / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: C095381:factor V Leiden; D005165:Factor V; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human