Cytokine polymorphisms and risk of infection after kidney transplantation.
BACKGROUND
Infection remains a significant cause of morbidity and mortality after solid organ transplantation. Genetic background has an influence on the incidence of infection. The aim of our study was to analyze the relationship between cytokine polymorphisms and infection in our kidney transplant recipients.


METHODS
DNA from 255 kidney transplant recipients was isolated routinely. Polymerase chain reaction sequence-specific primer was performed using commercially available cytokine genotyping primer packs to determine polymorphisms of interleukin (IL)-10, transforming growth factor-beta, tumor necrosis factor-alpha, interferon-gamma, IL-6, IL-4, IL-2, IL-12, IL-4R alpha, IL-1RA, IL-1R, IL-1 beta, and IL-1 alpha. The appearance and number of infections within the first year after transplantation were identified retrospectively.


RESULTS
One hundred twenty-two patients experienced at least one episode of infection in the first year after transplant. The frequency of the -511 IL-1beta CC genotype and the frequencies of the -1188 IL-12 CA and CC genotypes were significantly higher among the infected patients compared with the noninfected patients. We failed to observe significant differences in the genotype distribution of the other analyzed cytokines regarding the incidence of infection. After adjusting, recipient IL-1beta (-511 CC) genotype (relative risk [RR] 2.67, 95% confidence interval (CI) 1.30 to 5.49, P = .007) and recipient IL-12 (-1188 CA and CC) genotypes (RR 2.57, 95% CI 1.22 to 5.38, P = .012) predicted independently the risk of infection in the first year after kidney transplantation.


CONCLUSIONS
Kidney transplant recipients with -511 IL-1beta CC genotype or with -1188 IL-12 CA and CC genotypes were at higher risk of developing infections in the first year after transplantation. Patients with genetic susceptibility to infection may benefit from less potent immunosuppressive therapy and more intense preventive measures.
Rodrigo
E
E
Service of Nephrology, Hospital Valdecilla. University of Cantabria, Santander, Spain. nefrce@humv.es
Sánchez-Velasco
P
P
Ruiz
J C
JC
Fernández-Fresnedo
G
G
López-Hoyos
M
M
Piñera
C
C
Palomar
R
R
Gómez-Alamillo
C
C
González-Cotorruelo
J
J
Leyba-Cobián
F
F
Arias
M
M
D000328:Adult; D003062:Codon; D016207:Cytokines / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D007239:Infections / Q000453:epidemiology*; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology; D016212:Transforming Growth Factor beta / Q000235:genetics
D003062:Codon; D016207:Cytokines; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA