Carriers of Genetic Mutation at 1.7 Times Greater Risk for Multiple Sclerosis

Women with a specific genetic variation have a significantly greater chance of developing multiple sclerosis (MS), according to research published in the journal ASN Neuro.

Researchers from the University of Illinois at Chicago observed a family of 5 siblings in order to test the association between MS and the genetic variation which contributes to Peutz Jeghers Syndrome, a rare autosomal dominant disease caused by mutations in the serine threonine kinase 11 (STK11). The sisters were between the ages of 23 and 26 years, and all were diagnosed with MS. The variant was present in the 3 siblings (including twins) that were tested. Similar, but not identical, genetic variants were discovered in the other 2 siblings as well.

These findings were called “one of the strongest genetic risk factors for MS discovered to date,” by senior author Doug Feinstein, PhD, in a press release.

When study coordinator Anne Boullerne learned from a casual conversation with one of the women involved in the study that she and all 4 of her siblings had MS, she was intrigued.

“I was immediately interested in the possibility of a genetic study of the family because all 5 siblings — an entire generation – are affected by MS, and so we could have a very good chance of discovering key genes related to inheritance of the disease,” Boullerne said.

The researchers conducted a complete DNA sequencing of the original sibling’s genome, and closely examined the STK11 gene. The woman’s twin sisters carried the same genetic variant.

In the next phase of the study, the researchers wanted to determine if single nucleotide polymorphism (SNP), the genetic variant they had previously identified, in fact contributed to MS in the siblings. They screened DNA samples from 750 MS patients and 650 healthy patients. For women SNP carriers ,the prevalence of MS was 1.7 times higher than women without MS.

The researchers estimated that STK11 SNP is present in about 7 percent of the general population, based on extrapolations from their data. But, Feinstein said, far fewer people develop MS. This means that other factors play into risk and development of MS, and whether they are genetic or non genetic is yet to be determined.

The researchers next want to screen the DNA of the 5 siblings’ parents to continue looking for other genetic factors that contribute to MS. In the future, they will additionally investigate the purpose of the STK11 gene in the lab. They hope to pinpoint the molecular pathways involved in MS development.