The Relationship of JAM2 Polymorphisms and Graft-Versus-Host-Disease (GVHD) after Allogeneic Stem Cell Transplantation

Introduction: The junctional adhesion molecule 2 (JAM2) gene plays a key role in tight junction formation in epithelial and endothelial cell. We studied JAM2 polymorphism in GVHD and non-GVHD patients after allogeneic stem cell transplantation.

Methods: We tested 3 sites of JAM2 gene - rs2276220 (G/A), rs963103 (T/C), rs974680 (G/A) - and studied the possible link between the JAM2 polymorphism and the risk of GVHD. We studied 251 patients who had treated with allogeneic stem cell transplantation. The three-SNP block study was performed with rs2276220-rs963103-rs974680 haplotypes. The JAM2 gene was screened for polymorphisms by SNaPShot method. We used SAS version 8.1 (SAS Institute Inc., Cary, NC, USA) for statistic analysis. The odds ratio and p-value was adjusted with multiple logistic regression analysis about age, gender, stem cell source, disease status at the time of transplantation, and conditioning regimen.

Results: The minor allele C of rs963103 (T/C) was dominant in patients with acute GVHD (Odds ratio (OR) 2.918, 95% confidence interval (CI) 1.178~7.233; p=0.0207). This phenomenon was distinct in gut GVHD (OR 1.684, 1.019~2.784; p=0.0419). The minor allele A of rs2276220 (G/A) was dominant in patients with infection after allogeneic stem cell transplantation (OR 6.058, 1.266~28.979; p=0.0241). The overall survival (OS) was associated with rs2276220 (hazard ratio (HR) 0.887, 95% CI 0.633~1.242; p=0.0346) and rs974680 (HR 0.969, 0.763~1.23; p=0.0193). The progression-free survival (PFS) was associated with rs2276220 (HR 0.761, 0.544~1.064; p=0.0095) and rs974680 (HR 0.551, 0.274~1.108; p=0.0382). In three-SNP block study which was performed with rs2276220- rs963103-rs974680 haplotypes, ATA (HR 0.844, 0.645~1.105; p=0.0016) and GTA (HR 5.568, 1.686~18.384; p=0.0048) was associated with OS. ATA (HR 0.796, 0.559~1.133; p=0.0039) and GTG (HR 1.339, 0.834~2.149; p=0.0353) was associated with PFS.

Conclusions: The JAM2 gene polymorphism rs963103 was associated with acute GVHD especially with gut GVHD after allogeneic stem cell transplantation; with higher risk in carriers of the C allele. The JAM2 gene polymorphism rs2276220 was associated with infection, OS, and PFS after allogeneic stem cell transplantation; with higher risk in carriers of the A allele.