Newly ID’d Gene Variant Linked to Slower Progression of Systemic Sclerosis in Women in Small Study

A newly discovered genetic variant in the FOXP3 gene is associated with a slower progression of systemic sclerosis in women, a small Italian cohort study reports.

The research “FOXP3, ICOS and ICOSL gene polymorphisms in systemic sclerosis: FOXP3 rs2294020 is associated with disease progression in a female Italian population” was published in the journal Immunobiology.

While the causes of systemic sclerosis are not fully known, increasing data support some patients being genetically predisposed to developing it.

Previous studies have reported several polymorphisms — naturally occurring variants in the DNA sequence — in genes involved in key immune system cells in many autoimmune diseases, including systemic sclerosis.

A team of researchers analyzed how certain polymorphisms affected the susceptibility and progression of systemic sclerosis in a group of Italian patients.

The study enrolled 350 people (280 women and 70 men). Of them, 166 had systemic sclerosis and 184 were healthy controls. Using blood samples from each participant, researchers extracted and analyzed the DNA.

Researchers analyzed polymorphisms in three specific genes — FOXP3, ICOS and ICOSL – all important for regulating the workings of a group of immune cells called regulatory T-cells.

The single nucleotide polymorphisms analyzed were rs2294020 in FOXP3, rs6726035 in ICOS, and rs378299 in ICOSL.

Results showed no link between the single nucleotide polymorphisms analyzed and the participant’s susceptibility to developing systemic sclerosis.

However, the occurrence of the FOXP3 rs2294020 polymorphism was linked to slower disease progression of the disease in women.

No conclusions could be drawn for the susceptibility to the disease or the time to progression in men due to the low statistical power, the researchers said.

“This study provides evidence of the association of rs2294020 with SSc [systemic sclerosis] evolution in female patients, modulating the time of progression from the diagnosis of early SSc to the diagnosis of definite SSc, while no effect on SSc susceptibility per se was found,” they wrote.

The team believes that “rs2294020 may be considered a disease-modifying gene-variant rather than a disease-susceptibility SNP [single nucleotide polymorphism] in SSc.”

More studies are needed to characterize genetic variants involved in immune dysregulation and autoimmune diseases.