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Epigenetics is a natural occurrence in which modifications in gene expression are affected by environmental factors without any change in the DNA sequences. Several factors that can affect the gene expression in transplanted organs include drugs, nutrition, lifestyle, and environment. These factors may affect the transplanted organ’s cells, determining their longevity (Figure 80-1).


Schematic diagram of different stimuli contributing to epigenetic modifications, gene expression, and associated disease outcome.

Successful kidney transplantation is the best treatment preference for end-stage renal disease (ESRD) patients, improving individual patient longevity and quality of life. However, graft loss remains a serious concern, which may result in increased mortality. Epigenetic modifications may aggravate the genetic expression or independently affect the outcome of kidney transplantation. Although several studies presented the products of these interactions in terms of immunity and clinical manifestations, the occurrence of alterations in gene expression as a consequence of epigenetic modification has not been examined in general, particularly in kidney transplant patients.

Epigenetics is the mitotically and/or meiotically heritable modification in the gene expression molded by mechanisms that do not involve the general DNA nucleotide sequence change.1 Chromatin consists of DNA structural histone proteins and nonhistone proteins that may undergo various remodeling forms, leading to either facilitation or hindrance of transcription. First, DNA needs to be uncoiled from the histones to allow the transcription factors to bind to their corresponding sites2 as tight coiling of the DNA and a closed chromatin structure covering the binding site, preventing the transcription process initiation. Different chromatin epigenetic modifications include methylation or demethylation of the DNA and histone acetylation or deacetylation.3 DNA methylation acts by covalent transfer of methyl group to C-5 position carbon of cytosine ring catalyzed by DNA methyltransferase enzyme. DNA methylation is often associated with the silencing of the transcription process. Histone acetylation occurs at the histones’ amino-terminal tails that protrude from the nucleosomes, regulated by histone acetyl transferase (HAT) and histone deacetylases (HDAC) enzymes. HAT allows the unwinding of the chromatin structure, allowing transcription to occur. In contrast, HDAC coils the chromatin tightly around the histone, preventing gene transcription (Figure 80-2).


Mechanisms of inheritable epigenetics. Both genetic and epigenetic factors tightly regulate mammalian gene expression. Ac: Acetyl group; CpG: cytosine-phospho-guanosine; DNA: deoxyribonucleic acid; H3K27: histone 3 lysine 27; H3K9: histone 3 lysine 9; Me: methyl group.


In patients with ESRD, renal transplantation is the treatment of choice. However, late graft loss continues to be a significant concern after renal transplantation. Immunological and nonimmunological stressors, including ischemia-reperfusion (I/R) injury, infection, donor age, immunosuppressive drugs, and inflammation, determine overall cumulative damage manifesting in the form of the longevity of the graft and ...

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