Recipient genetic determinants of inflammatory process and nonstandard atherosclerosis risk factors affect kidney graft function early posttransplantation.
We analyzed the connections between recipient genetic features and 12-month graft function. The gene polymorphisms of myeloperoxidase (MPO), interleukin (IL)-1beta, IL-6, C-reactive protein (CRP), fetuin A, and homocysteine and their gene product concentrations were correlated with 12-month kidney transplant function. The 125 kidney recipients had at least 12 months of follow-up (average, 30.9 +/- 13.0 months). IL6-174G/C, IL1beta 3954C/T, MTHFR 677C/T, MTHFR 1298A/C, AHSG 1/2 SNPs were determined using SSP-polymerase chain reaction (PCR) and MPO-463G/A and CRP- 390C/T/A with RLFP analysis. Enzyme-linked immunosorbent assay (ELISA) was applied to estimate MPO, fetuin A, IL-6, and IL-1beta; FPIA was applied for L-homocysteine concentrations. The highest CRP values were linked to the presence of the TT genotype. We observed a positive correlation of CRP concentrations and GFR. Lower fetuin A concentrations were linked to the 256Ser allele, and higher levels to better graft function. Worse graft function was inversely associated with serum homocysteine concentrations. Two polymorphisms (CRP and fetuin A) showed functional consequences in recipients. None of the examined genetic determinations influenced long-term graft function. Higher values, although still within the normal range of CRP concentrations on the day of transplantation and 3 months thereafter, were related to greater values of eGFR at 12 months, suggesting that the higher intensity of the inflammatory reaction may be a manifestation of more effective healing of an ischemia reperfusion injury. Both homocysteine and fetuin A showed long-term prognostic importance.
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, ul. Traugutta 57/59, 50-417 Wroclaw, Poland. magda@softstar.pl
M
M
Krajewska
K
K
Kościelska-Kasprzak
W
W
Weyde
D
D
Drulis-Fajdasz
K
K
Madziarska
O
O
Mazanowska
M
M
Kusztal
M
M
Klinger
D019943:Amino Acid Substitution; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects / Q000502:physiology*; D009195:Peroxidase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology; D011184:Postoperative Period; D012307:Risk Factors; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D015850:Interleukin-6; D060749:alpha-2-HS-Glycoprotein; D006710:Homocysteine; D002097:C-Reactive Protein; D009195:Peroxidase