Slc11a1 (formerly Nramp1) polymorphisms and susceptibility to post-transplant lymphoproliferative disease following pediatric liver transplantation.
BACKGROUND
Polymorphisms of the solute carrier family 11 member 1 (Slc11a1) gene have previously been associated with susceptibility to infectious disease, anti-tumor defenses, and autoimmune diseases. We postulated that polymorphisms of the gene may also be associated with susceptibility to post-transplant lymphoproliferative disease (PTLD), a disease thought to be related to an impaired immune response to Epstein-Barr virus (EBV) in immunosuppressed patients.


METHODS
Whole blood samples were obtained from 45 pediatric patients who underwent liver transplantation. Polymerase chain reaction (PCR) was used to amplify a 3' region of the gene that includes an exon 15 single-nucleotide substitution (referred to as D543N) and a 4-bp deletion polymorphism (referred to as 3'-UTR). PCR products were digested using AvaII and FokI restriction enzymes for the D543N and 3'-UTR polymorphisms, respectively. PTLD disease status and EBV virus serum titers of all patients were obtained from hospital records.


RESULTS
Six of the 45 pediatric transplant recipients developed PTLD. An association was found between 3'-UTR polymorphisms of Slc11a1 and incidence of PTLD after liver transplantation (P = 0.005). In addition, post-transplant serum EBV titers were higher (P = 0.009) for recipients with certain Slc11a1 polymorphisms. No association was found between the D543N polymorphism and incidence of PTLD.


CONCLUSIONS
3'-UTR polymorphisms of the Slc11a1 gene appear to be associated with susceptibility to PTLD and the immune response to EBV in pediatric liver transplant recipients. Genotyping of pediatric patients undergoing liver transplantation may enable early identification of patients at high risk for developing high EBV titers and/or PTLD.
Barshes
N R
NR
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Lee
T R
TR
Goss
J A
JA
Goodpastor
S E
SE
Huls
M H
MH
Rooney
C M
CM
Karpen
S J
SJ
Wyllie
S
S
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology / Q000502:physiology*; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000821:virology; D008297:Male; D011110:Polymorphism, Genetic; D000099173:Natural Resistance-associated Macrophage Protein 1
D020413:3' Untranslated Regions; D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1