Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters.

Petr Ponomarenko,Ekaterina Sharypova,Nikolay L Podkolodny,Olga Podkolodnaya,Irina Chadaeva,Nikolay Kolchanov,Mikhail Ponomarenko,Natalya N Tverdokhleb,Ludmila Savinkova,Valentin Suslov,Dmitry Rasskazov

doi:10.1155/2016/8642703

Abstract

Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

Highlights

Diurnal oscillations of the expression level have been reliably identified in ∼10000 genes of placental mammals [1]
Let us review in detail these more comprehensively studied single nucleotide polymorphisms (SNPs) markers in order to briefly describe, in a similar fashion, the candidate SNP markers in the genes of human circadian clock core which were identified for the first time
We found three additional unannotated SNPs that can reduce expression of genes HBB and HBD and may serve as candidate SNP markers of these chronopathologies

Summary

Introduction

Diurnal (circadian) oscillations of the expression level have been reliably identified in ∼10000 genes of placental mammals [1]. The central circadian oscillator imposes a rhythm on peripheral oscillators, which share their molecular genetic structure but work in each cell in accordance with their own specific rhythms of organs, tissues, and systems of tissues [1] All these oscillators set the rhythm for a multitude of genes via expression of tissue-specific transcription factors (short-term regulation) or chromatin remodeling (long-term regulation) [6, 7]. We applied our Web service SNP TATA Comparator [35] to unannotated SNPs in binding sites of fjwhich are located near known SNP markers of Mendelian human diseases and, for this reason, can cause the same pathologies if these SNPs change the affinity of fjfor the same promoters of the same human genes. We identified 53 candidate SNP markers of human chronopathologies; validation of these markers in accordance with clinical standards may make these SNPs useful for predictive-preventive personalized medicine [41]

Methods

Results and Discussion

Conclusions