ASSOCIATIONS BETWEEN OBESITY-RELATED FTO rs9939609, PPARS GENE VARIANTS AND KIDNEY TRANSPLANTATION

Obesity and lipid abnormalities have implications in various post-transplant pathological conditions, including infections, cardiovascular and metabolic diseases and chronic rejection. Some gene polymorphisms involved in metabolic processes, that could increase the medication-related post transplant risk, are poorly investigated in organ transplantation. FTO (fat mass and obesity-associated) gene variants affect obesity susceptibility in the general population; PPARs (peroxisome proliferator-activated receptors) are nuclear receptors both involved in lipid metabolism, insulin sensitization, inflammation and immune regulation. To evaluate if they could be additional risk factors for post transplant outcome, their associations with pre-post transplant clinical parameters were analyzed. Polymorphisms of FTO rs9939609, PPARA rs1800206 (Leu162Val), PPARG rs1801282 (Pro12Ala) and PPARD rs2016520 were detected using Taqman allelic discrimination methods. Variations of BMI, blood lipids, fasting plasma glucose and creatinine levels were examined in association with genotypes in 173 kidney transplant recipients. Results show that pre-transplant and post-transplant total cholesterol was increased in patients carrying the C allele of the PPARD rs2016520 polymorphism (pre-transplant: C/C + C/T, 190.18 43.23 mg/dl, T/T, 164.62 42.51 mg/dl, p = 0.001; 1 year after transplantation: C/C + C/T, 206.73 47.42 mg/dl, T/T, 192.16 35.10 mg/dl, p = 0.01). No other significant associations were found, although a trend to a slight increase of FTO A/A genotype frequency in obese patients in the first/second years after transplantation was present (1 year, obese, A/A = 34.8%, non obese 19.3%, p = ns). In conclusion, analyzing a possible impact of the examined gene variants on some of the main post transplant risk factors for cardiovascular and metabolic diseases, only slight effects of FTO rs9939609 on the increase of body mass/obesity were detected; an association of PPARD rs2016520 with hypercholesterolemia in the early post-transplant period gives the indication for deeper investigations in the view of possible personalized interventions.