Genes regulating the growth factor VEGF signaling pathway are linked to the presence of mouth ulcers in people with systemic lupus erythematosus (SLE), according to a study presented at the European League Against Rheumatism Annual Congress (EULAR 2016) in London on June 10. The finding gives scientists a clue of disease processes at work, and will help to focus research into this specific lupus manifestation.
Various lupus manifestations are likely linked to specific disease mechanisms, and recent studies suggest that they are tied to specific genetic alterations. The research team performed a genome-wide association study, examining if point mutations across the genome linked to specific genetic pathways might explain the occurrence of various symptoms.
Researchers screened 482 lupus patients of Southern European origin, looking at the presence of 598,258 point mutations called SNPs (pronounced Snips), belonging to 700 genetic pathways. They attempted to see if any of these pathways could be linked to 14 disease manifestations.
“Understanding the relationships between specific SLE risk genes and different manifestations of the disease should help elucidate the underlying disease mechanisms and pathways,” the study’s lead author, Dr. Antonio Julià from the Vall d’Hebron Research Institute, Barcelona, Spain, said in a news release. “Understanding more about the genetic pathways which underlie different manifestations of SLE is an important step towards the goal of improving the management of SLE, and ultimately to offer preventative care to individuals at increased risk of SLE.”
Patients from 15 Spanish hospitals were enrolled in the study, “Genome-Wide Pathway Analysis Reveals That VEGF Genetic Pathway is Associated With Oral Ulcers in Systemic Lupus Erythematosus,” in what was termed a discovery phase — the initial stage of a gene association study. The team found two genetic pathways linked to mouth ulcers and antinuclear antibodies.
Since genetic association studies often produce false positive results, repeating the process in another group of patients is crucial for validating a finding. Therefore, the team recruited another 425 individuals, and confirmed the association between mouth ulcers and the VEGF gene pathway. The link to antinuclear antibodies, however, was not found in this second group of patients.
“[A]nalyzing the transcriptional effect of the topical immunotherapies used for the treatment of mouth ulcers in SLE, we found a significant differential expression of VEGF pathway genes,” Dr Julià said.