Stromal Cell-Derived Factor 1 Gene Polymorphism Is Associated with Susceptibility to Adverse Long-Term Allograft Outcomes in Non-Diabetic Kidney Transplant Recipients

Abstract

Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1) is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal transplant recipients (RTRs). Baseline characteristics and blood chemistry were recorded. Genomic DNA extraction with polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze the genetic polymorphisms of SDF-1 (rs1801157). The influence of SDF-1 on an adverse renal allograft outcome, defined as either a doubling of serum creatinine, graft failure, or patient death was evaluated. Sixteen patients with the SDF-1 AA/AG genotype and nine with the SDF-1 GG genotype reached an adverse outcome. According to Kaplan-Meier analysis, patients carrying the SDF-1 AA/AG genotype or A allele showed a significantly higher risk of reaching an adverse outcome than those carrying the SDF-1 GG genotype or G allele (p = 0.041; p = 0.0051, respectively; log rank test). Stepwise multivariate Cox proportional regression analysis revealed that patients carrying the SDF-1 AA/AG genotype and A allele had a 2.742-fold (95% CI. 1.106–6.799, p = 0.03) and 2.306-fold (95% CI. 1.254–4.24, p = 0.008) risk of experiencing an adverse outcome. The SDF-1 AA/AG genotype and A allele have a detrimental impact on the long-term outcome of RTRs.

The Role of CXCL12 in Kidney Diseases: A Friend or Foe?

“…Both Lee et al [57] and Wang et al's. [58] teams proposed that AA/AG genotype and an allele of CXCL12 had adverse effects on the endpoint of allograft kidney transplantation. Therefore, genetic effects from donors should be carefully considered in order to select appropriate donors in kidney transplantation.…”

Dual role of the CXCL12 polymorphism in patients with chronic lymphocytic leukemia

“…The CXCL12 rs1801157 polymorphism, comprising a guanine to adenine transition in the 3′ untranslated region (3′UTR), has been widely studied regarding its potential role in malignancy disorders, such as multiple myeloma , acute lymphoblastic leukemia , non‐Hodgkin's lymphoma , breast cancer , esophagogastric cancer , hepatocellular carcinoma and some others. There is also a number of studies documenting the association of this single nucleotide polymorphism (SNP) with the outcome of organ and hematopoietic stem cells transplantation . Our previous studies showed the association of the CXCL12‐3′A variant with the G‐CSF‐induced mobilization potential of CD34 progenitors from the bone marrow to the peripheral circulation in autologous transplant recipients as well as in healthy donors of allogeneic transplants.…”