STUDY OF RS4253778 POLYMORPHISM RELATED TO PEROXISOME PROLIFERATOR ALPHA RECEPTOR GENE IN RAPAMYCIN-TREATED KIDNEY TRANSPLANT RECIPIENTS IN WEST AZARBAIJAN PROVINCE (IRAN)

Rapamycin (sirolimus) is one of the immunosuppressive drugs that has a strong immunosuppressive effect and one of the factors that inhibits mTOR. The drug rapamycin is used in the prevention of kidney transplant rejection in kidney transplant recipients. Sirolimus is not only an inhibitor of the target of rapamycin, but also a substrate for cytochrome P450 enzyme subfamilies and for multidrug efflux pumps. The results of recent studies have shown that peroxisomal proliferation activating receptors, as a group of nuclear receptors, have multiple cellular effects and their genetic polymorphisms in connection with other genes play an important role in creating human immune system responses. The aim of this study was to determine the peroxisome proliferator alpha gene polymorphism in kidney transplant recipients treated with rapamycin and healthy controls in West Azerbaijan province (Iran) and compare them with each other.

In this case-control study, 40 kidney transplant recipients treated with rapamycin one mg(as case group) and 63 healthy controls as control group were evaluated. Samplings were done in the kidney transplant clinic of Imam Khomeini Hospital (Urmia) under the supervision of a kidney specialist. The salting out method was used to genomic DNA isolation. PCR products were analyzed after enzymatic cleavage with Taq® enzyme. Data were obtained by direct counting of observed alleles and genotypes as well as the total number of samples. Then chi-square test or Fisher's exact test was used to analyze the results in the 2x2 table. The significant difference between the two groups was considered equal to 0.05.

The frequency of homozygous G/G PPARα rs4253778 genotype and heterozygous G/C PPARα rs4253778 genotype observed in the healthy control group of the present study was 40 (63.49%) and 23 (36.51%) respectively. The homozygous C/C PPARα rs4253778 genotype was not observed in the healthy control group. The frequency of homozygous genotype G/G, heterozygous genotype G/C and homozygous genotype C/C in PPAR α rs4253778 Biomarker in the patient group was 29 (72.5%), 9 (22.5%) and 2 (5%) respectively. Comparison of the desired frequencies in the two groups showed that there is no statistically significant difference (P > 0.05). The frequency of G and C alleles in the patient group is 0.84 and 0.16, respectively; and in healthy control it is equal to 0.81 and 0.19 respectively.

In the present study, we concluded that there was no significant relationship between PPARα rs4253778 G>C polymorphism and the use of low concentration of rapamycin. Further study with more samples related to the topic is recommended.