Genetic Variability of Major Inflammatory Mediators Has No Impact on the Outcome of Kidney Transplantation

Abstract

In contrast to previous allelic association studies, neither of the polymorphisms has been associated with the outcome of kidney transplantation in the single locus analysis nor in the haplotype model. Our findings reinforce the need for more rigorous research compliant with the currently accepted standards for polymorphism-disease association studies.

Genetic polymorphisms in the immune response: A focus on kidney transplantation

“…Brabcova and colleagues typed 9 loci in immune system genes TNFA rs1800629 (− 308), CCL2 rs1024611 (− 2518), CCL5 rs2107538 (− 403), − 109 (no rs reported) and rs2280788 (− 28), CCR2 rs1799864 (+ 190G/A), IFNG rs2430561 (+874A/T), TGFB1 rs1800470 (c10) and rs1800471 (c25) (total number of recipients = 436; chronic allograft nephropathy cases = 122, cases with sub-clinical rejection = 38, acute rejection cases = 190), and found no associations [53] (Tables 2 and 3). Sánchez-Velasco and colleagues genotyped IL6 rs1800795 (−174) in 335 kidney recipients (cases of acute rejection = 133, cases of chronic allograft nephropathy = 115) and found no associations [54] (Tables 2 and 3).…”

Citocinas e quimiocinas no transplante renal

“…35,36 IP-10/CXCL10, MIG/CXCL9, CXCR3, RANTES/ CCL5 e o percentual de ligação de IL-2 relacionaramse com a ocorrência de RA. 47 [70][71] A Tabela 2 resume os principais estudos sobre polimorfismo genético de citocinas/quimiocinas em transplantados renais.…”

Genetic Variations and Transplant Outcomes

“…Donor TNF-α genotypes for 244 patients (–308 G/A), as well as in 965 patients (rs3093662) showed a significant association with acute rejection [4,12]; however, these findings were not confirmed in another cohort of 436 transplant recipients [13]. …”

“…Different SNPs in proinflammatory mediators including TNF-α, MCP-1 or RANTES, were analyzed in 436 patients for their impact on chronic allograft nephropathy, but no effect was found [13]. A smaller study with 157 patients demonstrated, in a subgroup with prevalent acute rejection episode, a significantly worse graft survival in patients with acute rejection bearing the TNF-α high producer genotype [27].…”

“…Three polymorphisms within the promoter (–403G/A, –109T/C, –28G/C) and one within the first intron were associated with higher protein expression with an impact on acute [13] or recurrence of acute rejection [16]. …”