Cytokine gene polymorphisms predict acute rejection following renal transplantation

Cytokine gene polymorphisms predict acute rejection following renal transplantation

International Congress Series 1255 (2003) 99 – 100 Cytokine gene polymorphisms predict acute rejection following renal transplantation Lei Yang *, Yo...

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International Congress Series 1255 (2003) 99 – 100

Cytokine gene polymorphisms predict acute rejection following renal transplantation Lei Yang *, Yongfeng Liu General Surgery and Organ Transplant Unit, Organ Transplantation Institute, First Clinical University Hospital, China Medical University, Shenyang 110001, China Received 27 February 2003; accepted 28 March 2003

Abstract Background and methods: To study cytokine interleukin 10 (IL-10) gene promoter 1082 and tumor necrosis factor alpha (TNF-a) gene promoter 308 position polymorphisms predicting acute graft rejection following renal transplantation, we measured IL-10 and TNF-a production of peripheral blood cells by enzyme-linked immunosorbent assay. Results: The recipient with A/A or A/ G genotype in TNF-a promoter 308 position secretes more cytokine than those with G/G (Table 1). IL-10 genotypes were G/G, A/G and A/A. Recipients with G/G genotype secrete more cytokine than those with A/G or A/A (Table 2). When HLA-DR mismatched, the recipient with TNF-a high producer genotype (TNF2+) or IL-10 G/G genotype showed higher occurrence of acute rejection. Conclusions: TNF-a and IL-10 gene promoter polymorphisms have significant relationship with cytokine production of peripheral blood cells, the recipients with high producer genotype are inclined to occurrence of acute rejection. D 2003 Elsevier B.V. All rights reserved. Keywords: Gene polymorphisms; Interleukin 10 (IL-10); Tumor necrosis factor alpha (TNF-a); Acute rejection; Renal transplantation

1. Background and methods To study cytokine interleukin 10 (IL-10) gene promoter 1082 and tumor necrosis factor alpha (TNF-a) gene promoter 308 position polymorphisms predicting acute graft rejection following renal transplantation, we measured IL-10 and TNF-a production of * Corresponding author. 155 North Nanjing Street, Shenyang, Liaoning Province, China. Tel.: +86-2423256666x6235; fax: +86-24-23265539. E-mail address: [email protected] (L. Yang). 0531-5131/03 D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0531-5131(03)00675-7

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L. Yang, Y. Liu / International Congress Series 1255 (2003) 99 – 100

Table 1 The association between TNF-a gene polymorphism and production of TNF-a in vitro TNF-a genotype

A/A

A/G

G/G

TNF-a (pg/ml)

624.96 F 177.78

544.32 F 132.42

233.16 F 25.37*

* p < 0.01 compared with A/A. Table 2 The association between IL-10 gene polymorphism and production of IL-10 in vitro IL-10 genotype

G/G

A/G

A/A

IL-10 (pg/ml)

571.88 F 77.76

316.20 F 75.72*

269.68 F 28.52*

* p < 0.01 compared with G/G.

peripheral blood cells by enzyme-linked immunosorbent assay and determined their IL-10 gene promoter 1082 and TNF-a gene promoter 308 polymorphisms by PCR restriction fragment length polymorphisms (PCR-RFLP) in 35 preoperative recipients. The association between TNF-a and IL-10 promoter polymorphisms and production of them was studied. Furthermore, the correlation between their polymorphisms and acute rejection in first 3 months after renal transplantation was discussed.

2. Results The recipient with A/A or A/G genotype in TNF-a promoter 308 position secreted more cytokine than those with G/G (Table 1). IL-10 genotypes were G/G, A/G and A/A. Recipients with G/G genotype secrete more cytokine than those with A/G or A/A (Table 2). Patients with acute rejection have higher IL-10 level than those without rejection. When HLA-DR mismatched, the recipient with TNF-a high producer genotype (TNF2+) or IL-10 G/G genotype showed higher occurrence of acute rejection than those with low producer genotype in the first 3 months after renal transplantation (Table 3).

3. Conclusions TNF-a and IL-10 gene promoter polymorphisms have significant relationship with cytokine production of peripheral blood cells, recipients with high producer genotype are inclined to occurrence of acute rejection.

Table 3 The association between gene polymorphisms of TNF-a, IL-10 and acute rejection after kidney transplantation Genotype

Phenotype

Acute rejection

No acute rejection

p

TNF2 + TNF2 IL-10A IL-10A +

high low high low

5 2 4 3

5 23 4 24

0.012 0.033