PMID- 32228494 OWN - NLM STAT- MEDLINE DCOM- 20210907 LR - 20210907 IS - 1471-2369 (Electronic) IS - 1471-2369 (Linking) VI - 21 IP - 1 DP - 2020 Mar 30 TI - HLA-G14bp ins/del polymorphism and post-transplant weight gain in kidney transplantation: potential implications beyond tolerance. PG - 109 LID - 10.1186/s12882-020-01752-6 [doi] LID - 109 AB - BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical HLA molecule with immunomodulant and immunosuppressive functions, involved in transplantation tolerance. HLA-G14bp ins/del polymorphism in exon 8 has been associated with allograft rejection and kidney transplant outcome, with controversial results. We investigated associations of HLA-G14bp ins/del polymorphism on onset of some of the main post-transplant risk factors, like excess body weight, lipid abnormalities, increased fasting plasma glucose. Polymorphisms of cytokines with both immunosuppressive and metabolic effects were also assessed for comparisons and associated analysis. METHODS: The present study involved kidney transplant recipients (n = 173) in which body mass index, cholesterol, triglycerides, fasting plasma glucose were registered in the first years after transplantation and analyzed in association with genotypes. Presence of hypertension and smoking habits, demographic, transplant-related and therapeutic data of patients were also recorded. Polymerase chain reaction, sequence-specific primer amplification and Taqman allelic discrimination techniques were used for genotyping of HLA-G14bp ins/del, interleukin (IL)-10(-1082G > A,-819 T > C,-592A > C), transforming growth factor-beta(+ 869 T > C,+915C > G), IL-6(-174G > C), tumor necrosis factor-alpha(-308G > A) and IL-18(-137G > C,-607C > A). Effects of genotypes on clinical markers at each time point (pre-transplant and 1 to 5 years after transplant) were analyzed using a repeated-measures general linear model analysis; adjustment for potential confounders was performed. RESULTS: Results showed that HLA-G14bp ins/ins was significantly associated with obesity, in particular after transplantation (3 years, p = 0.002, OR = 4.48, 95% CI:1.76-11.41). Post-transplant body mass index was significantly increased in HLA-G14bp ins/ins carriers (3 and 4 years, p = 0.033 and p = 0.044); effects of HLA-G14bp genotypes on post-transplant BMI were confirmed by using repeated-measures analysis and after controlling for confounding variables. Cytokine genotypes did not associate with the examined factors. CONCLUSIONS: The study of transplanted patients allowed to evidence a potential relationship between post-transplant weight gain and HLA-G14bp ins/del polymorphism, previously involved in rejection for its immunosuppressive/tolerogenic activity. This novel association could widen the knowledge of the role and functions of HLA-G molecules in diseases and transplantation. FAU - Piancatelli, Daniela AU - Piancatelli D AD - National Research Council (CNR) - Institute of Translational Pharmacology (IFT), Via Carducci, 32, 67100, L'Aquila, Italy. daniela.piancatelli@cnr.it. FAU - Maccarone, Daniela AU - Maccarone D AD - Regional Center for Organ Transplantation (CRT), S. Salvatore Hospital, L'Aquila, Italy. FAU - Colanardi, Alessia AU - Colanardi A AD - National Research Council (CNR) - Institute of Translational Pharmacology (IFT), Via Carducci, 32, 67100, L'Aquila, Italy. FAU - Sebastiani, Pierluigi AU - Sebastiani P AD - National Research Council (CNR) - Institute of Translational Pharmacology (IFT), Via Carducci, 32, 67100, L'Aquila, Italy. FAU - Clemente, Katia AU - Clemente K AD - General Surgery and Organ Transplantation, S. Salvatore Hospital, L'Aquila, Italy. FAU - Iesari, Samuele AU - Iesari S AD - Pole de chirurgie experimentale et transplantation, Institut de recherche experimentale et clinique, Universite catholique de Louvain, Brussels, Belgium. AD - Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. FAU - Lai, Quirino AU - Lai Q AD - Transplant Unit, University "La Sapienza", Rome, Italy. FAU - Pisani, Francesco AU - Pisani F AD - General Surgery and Organ Transplantation, S. Salvatore Hospital, L'Aquila, Italy. AD - Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. LA - eng GR - not applicable/Consiglio Nazionale delle Ricerche/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200330 PL - England TA - BMC Nephrol JT - BMC nephrology JID - 100967793 RN - 0 (Cytokines) RN - 0 (HLA-G Antigens) RN - 0 (Immunologic Factors) SB - IM MH - Body Mass Index MH - *Cytokines/analysis/classification/genetics MH - Female MH - Genetic Predisposition to Disease MH - *Graft Rejection/genetics/immunology MH - *HLA-G Antigens/genetics/immunology MH - Humans MH - Immune Tolerance MH - Immunologic Factors/physiology MH - Kidney Transplantation/*adverse effects MH - Male MH - Middle Aged MH - *Obesity/diagnosis/etiology/immunology MH - Polymorphism, Genetic MH - *Postoperative Complications/diagnosis/genetics/immunology MH - Transplant Recipients/statistics & numerical data MH - Transplantation Immunology/genetics MH - *Weight Gain/genetics/immunology PMC - PMC7104538 OTO - NOTNLM OT - Gene polymorphism OT - HLA-G OT - Immunogenetics OT - Kidney transplant OT - Obesity COIS- The authors declare that they have no competing interests. EDAT- 2020/04/02 06:00 MHDA- 2021/09/08 06:00 PMCR- 2020/03/30 CRDT- 2020/04/02 06:00 PHST- 2019/10/30 00:00 [received] PHST- 2020/02/28 00:00 [accepted] PHST- 2020/04/02 06:00 [entrez] PHST- 2020/04/02 06:00 [pubmed] PHST- 2021/09/08 06:00 [medline] PHST- 2020/03/30 00:00 [pmc-release] AID - 10.1186/s12882-020-01752-6 [pii] AID - 1752 [pii] AID - 10.1186/s12882-020-01752-6 [doi] PST - epublish SO - BMC Nephrol. 2020 Mar 30;21(1):109. doi: 10.1186/s12882-020-01752-6.