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Donor PPAR? Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients: A Strobe-Compliant Observational Study.

ABSTRACT: Peroxisome proliferator-activated receptor ? (PPAR?) is an important regulator of glucose and lipid metabolism, and is predominantly expressed in the liver. We aimed to evaluate the effect of donor hepatic PPAR? gene polymorphisms on the development of metabolic disorders following liver transplantation (LT).A total of 176 patients undergoing primary LT were included in this Review Board-approved study. Genomic DNA was extracted from fresh frozen donor liver tissues (biopsy specimens for pathological testing at surgery). Eight single nucleotide polymorphisms in the PPAR? gene were chosen from either the HapMap CHB database or previous reports.The distribution of metabolic disorders differed significantly between the wild-type and variant genotypes of both the rs5767743 and rs5767700 loci (P < 0.05 for all). After an adjustment for other factors (body mass index and tacrolimus blood concentration), the rs5767743 genetic variant was found to be an independent protective factor (P = 0.005, odds ratio = 0.416 per C allele, 95% confidence interval? = 0.225-0.768). When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPAR? and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPAR? gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression.

SUBMITTER: Ling Q

PROVIDER: S-EPMC4616503 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients: A Strobe-Compliant Observational Study.

Ling Qi Q Xu Xiao X Wang Kai K Wang Chao C Xiang Penghui P Zhang Xuanyu X Zhuang Runzhou R Xie Haiyang H Zheng Shusen S

Medicine 20150901 35

Peroxisome proliferator-activated receptor α (PPARα) is an important regulator of glucose and lipid metabolism, and is predominantly expressed in the liver. We aimed to evaluate the effect of donor hepatic PPARα gene polymorphisms on the development of metabolic disorders following liver transplantation (LT).A total of 176 patients undergoing primary LT were included in this Review Board-approved study. Genomic DNA was extracted from fresh frozen donor liver tissues (biopsy specimens for patholo ...[more]

PMID: 26334901

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Project description:Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction-restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.

Dataset Information

Donor PPAR? Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients: A Strobe-Compliant Observational Study.

Publications

Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients: A Strobe-Compliant Observational Study.

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