Identifying Changes in Punitive Transcriptional Factor Binding Sites Created by PPAR&amp;lt;i&amp;gt;α/δ/γ&amp;lt;/i&amp;gt; SNPs Associated with Disease

Norman E Buroker

doi:10.4236/jbm.2017.54008

Abstract

Single nucleotide polymorphisms (SNPs) located in the PPARα/δ/γ genes that have been previously found to be significantly associated with human disease or a condition were also found to alter the genes punitive transcriptional factor binding sites (TFBS). Two alleles (C/G) of the PPARα SNP (rs1800206) were found to generate 7 common and 8 unique punitive TFBS. One of the unique TFBS created by the minor G (0.02) allele is for the T-Box 4 (TBX4) transcription factor which is associated with heritable pulmonary arterial hypertension. Two alleles (A/G) of the PPARδ SNP (rs2016520) were found to generate 20 unique punitive TFBS while the two alleles (C/G) of the PPARδ SNP (rs9794) were found to generate 11 common and 11unique punitive TFBS. The alleles of the PPARγ SNPs (rs10865710, rs12629751, rs709158, rs1805192 and rs3856806) were found to generate 15, 12, 16, 2 and 21 common and 9, 4, 12, 4 and 7 unique punitive TFBS, respectively. These changes in TFBS are discussed with relation to alterations in gene expression that may result in disease or change in human condition.

Highlights

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcriptional factors (TFs) that regulate many genes in cell differentiation and various metabolic processes including lipid and glucose homeostasis
Single nucleotide polymorphisms (SNPs) located in the PPARα/δ/γ genes that have been previously found to be significantly associated with human disease or a condition were found to alter the genes punitive transcriptional factor binding sites (TFBS)
One of the unique TFBS created by the minor G (0.02) allele is for the T-Box 4 (TBX4) transcription factor which is associated with heritable pulmonary arterial hypertension

Summary

Introduction

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcriptional factors (TFs) that regulate many genes in cell differentiation and various metabolic processes including lipid and glucose homeostasis. They are nuclear hormone receptors belonging to a steroid receptor superfamily that include estrogen, thyroid hormone, vitamin D3 and glucocorticoid receptors [1] [2] [3]. Buroker 82 three different genes found on chromosomes 22, 6 and 3, respectively These isotypes modulate the expression of several genes which play a central role in regulating glucose, lipid and cholesterol metabolism [4]. There has been much published concerning the PPARs significant involvement in the progression of human disease [1] [3] [6] [7] [8]

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Results

Conclusion