Porphyromonas gingivalis induced expression quantitative trait loci (eQTL) in humane monocytes

• Applicant: Professorin Dr. Lina Gölz
• Subject Area: Dentistry, Oral Surgery
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397619438

Modern technology has enabled integrative analysis of genome (DNA) and transcriptome (RNA) data leading to expression quantitative trait locus- (eQTL-) studies. These correlate alleles or genotypes of genetic variants with the quantitative expression of transcripts and allow the identification of gene variants which result in deviating expression of gene products. Recently genome- and transcriptome-wide eQTL-studies are feasible following exogenous stimulation. The objective of the present grant proposal is an eQTL-analysis in human monocytes activated with stimuli relevant for periodontitis. Periodontitis (inflammation of the tooth-supporting tissue) is a prevalent disease where the inflammatory surface area may correspond to the area of an ulcer of the size of the palm of the hand. In addition, periodontitis is associated with systemic diseases. Besides periodontal pathogen infection e.g. with Porphyromonas gingivalis (P.g.), genetic disposition is decisively involved in the development of periodontitis. P.g. is a gramnegative anaerobe and its most important virulence factor Lipopolysaccharide (LPS) activates specific receptors of the innate immune system, which occur in high density on the outer membrane of immune cells such as monocytes. The latter play a pivotal role in the pathogenesis of periodontitis and in that of systemic diseases. In the course of the scheduled research project, unstimulated monocytes will be compared with LPS P.g. stimulated monocytes. Within the framework of a start-up intramural funding, it was already possible to recruit more than 160 healthy subjects and to isolate and characterize their monocytes. In the project phase now requested, RNA from both monocyte fractions and DNA from the whole blood of the subjects are to be isolated. RNA samples will then be analyzed transcriptome-wide and the DNA samples will be genome-wide genotyped. Subsequently, eQTL-analysis can be performed and eQTLs are going to be identified which are specific for LPS P.g. stimulation. Further analysis will detect specific eQTLs of the LPS P.g.-stimulated monocytes which allow detailed insights into the pathophysiology of periodontitis. The transcripts and pathways should be very important for the development of new treatment strategies and biomarkers for periodontitis prediction and prognosis. Moreover, these pathways may also be crucial for associated systemic diseases. The eQTL-analyses applied here are scientifically innovative and are carried out in cooperation with several institutions of the medical faculty of Bonn. Together with her co-operation partners, the applicant was already able to establish all the methodologies and to publish first preliminary data. These form the basis for the present research application, which includes the necessary material funds to finance the cost-intensive eQTL-analysis. In the long-term, the applicant plans to establish a new focus on -eQTL in dentistry- at the medical faculty of Bonn.

• DFG Programme: Research Grants
• Co-Investigators: Privatdozent Dr. Michael Knapp; Professor Dr. Heiko Rühl