Interleukin 8 -251T>A and Interferon gamma +874A>T polymorphism: potential predictors of allograft outcome in renal transplant recipients from north India.
BACKGROUND
Episodes of acute rejection represent an important risk factor for the development of chronic allograft nephropathy. We explored whether certain cytokine gene polymorphisms in renal transplant recipients may be useful markers for susceptibility to allograft rejection. Interleukin 8 (IL8) -251 T>A and interferon gamma (IFNG) +874A>T gene polymorphisms were correlated with allograft outcome in renal transplant recipients.


METHODS
Genotyping was done by amplification refractory mutational system-polymerase chain reaction (ARMS-PCR) in 264 healthy controls and 296 renal transplant recipients categorized into 235 non-rejecters and 61 rejecters.


RESULTS
IL8 -251AA genotype was associated with 2.7-folds increased risk for allograft rejection in recipients experiencing rejection episodes as compared to non-rejecters (OR=2.70, P=0.032). Cox proportional analysis revealed >2-folds increased susceptibility for allograft rejection (HR=2.38, P=0.010) in IL8 -251AA recipients. Kaplan-Meier analysis also demonstrated lower mean time to first rejection episode for IL8 -251AA recipients (23 months) as compared to TT recipients (30 months) (log rank P=0.022). No association of IFNG +874A>T was observed with allograft rejection, however, an increasing trend towards immunosuppressant toxicity was observed in patients with +874TT genotype at one month post transplantation.


CONCLUSIONS
Thus, IL8 -251AA genotype may serve as potential predictor of allograft outcome in our North Indian cohort of renal transplant recipients.
Singh
Ranjana
R
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Kesarwani
Pravin
P
Ahirwar
Dinesh K
DK
Kapoor
Rakesh
R
Mittal
Rama D
RD
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007194:India; D007371:Interferon-gamma / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014184:Transplantation, Homologous
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016209:Interleukin-8; D007371:Interferon-gamma