Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation

Abstract

Background We aimed to examine whether combined donor/recipient variants in the leptin receptor ( LEPR ) and adiponectin ( ADIPOQ ) genes may affect outcomes in renal transplantation. Methods A total of 233 donors and their corresponding 307 recipients were genotyped for LEPR rs1805094, rs1137100 and rs1137101, and ADIPOQ rs1501299 and rs224176. Combined donor/recipient genetic scores were created to investigate associations with delayed graft function (DGF), graft loss and estimated glomerular filtration rate (eGFR). Results Recipients whose donors carried variant alleles of LEPR rs1137100 and rs1137101 had lower risk of DGF [OR = 0.48 (0.24–0.97), p = 0.040] and [OR = 0.47 (0.23–0.95), p = 0.035], respectively. In addition, rs1137101 also showed an inverse association with lower incidence of graft loss [OR = 0.44 (0.31–0.97), p = 0.040]. The analysis of genetic scores of donor/recipients showed that again rs1137101 was inversely associated with both outcomes: OR = 0.46 (0.23–0.92), p = 0.029 and OR = 0.45 (0.11–0.81), p = 0.009, respectively. With regard to graft function, the T-allele of ADIPOQ rs1501299 in the donor was related to higher eGFR values (75.26 ± 29.01 vs. 67.34 ± 25.39 ml/min for wild-type grafts, p = 0.012). Higher combined genetic scores in this same polymorphism were also associated with better function (78.33 ± 31.87 vs. 68.25 ± 24.32 ml/min, p = 0.018). Finally, eGFR values were similar between paired kidneys but they were different when comparing grafts with or without the rs1501299 T-variant (77.87 ± 26.50 vs. 69.27 ± 26.73 ml/min, p = 0.016). Conclusions Our study has shown for the first time to our knowledge that variants in LEPR and ADIPOQ genes of the donors and/or their combination with those in the recipients may affect the outcome of renal transplantation.

Serum adiponectin and cortisol levels are not affected by studied ADIPOQ gene variants: Tehran lipid and glucose study

“…Many studies demonstrated the association of SNP rs1501299 in adiponectin gene with adiponectin levels [ 19 , 25 ], but no association was found between rs1501299 and adiponectin levels in Italy [ 4 ] and Iran [ 35 ]. Studies have shown that SNP rs1501299 is associated with higher serum levels of Adiponectin [ 43 ], and it is a protective factor for diabetes Mellitus, hypertension, coronary artery disease, and dyslipidemia in American, Japanese, Finnish [ 35 ], and Korean populations [ 35 , 39 ]. No significant association was found between rs17366743 SNP and adiponectin concentration in Russian Federation [ 36 ].…”

Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients

“…Logistic regression modeling was used to examine the influence of the SNPs on vascular CKD risk, adjusting for demographics and classic risk factors, namely age, sex, ethnicity, diabetes and hypertension, as formerly described [ 38 ]. After testing five inheritance models in the preliminary genetic analyses (codominant, dominant, recessive, overdominant, and log-additive), we decided to utilize the dominant model in the risk analysis, as we have done in former reports by our group [ 39 , 40 ], because the resulting genotype groups were the most balanced in terms of size and because it resulted in more significant associations. In order to examine the value of the studied SNPs in predicting susceptibility to CKD, receiving operating curves (ROC) were generated for models containing classic clinical and demographic risk factors adding or not the genetic information.…”

Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy

“…It has been recently published by Mann et al that nearly one-third of pediatric renal transplant recipients had a genetic cause of their kidney disease identified by WES [ 22 ]. For the first time, Mota-Zamorano and colleagues found that some variants in the LEPR and ADIPOQ genes of donors and recipients might affect the outcome of kidney transplantation [ 23 ]. Later, it was observed in several studies that ADIPOQ played an essential role in patients with post-transplant diabetes mellitus [ 24 , 25 , 26 , 27 , 28 ].…”