Each Major Risk Factor (Like Genes, Smoking and Obesity) Can Affect Disease Course, Study Finds

Risk factors often associated with multiple sclerosis (MS), such as genetic background, obesity and smoking, contribute independently to the disease’s variability and may be an early influence on progression, a study reported.

The retrospective study, “Multiple sclerosis risk factors contribute to onset heterogeneity,” was published in the journal Multiple Sclerosis and Related Disorders.

MS, a neurodegenerative and autoimmune disease, is associated with both genetic and environmental risk factors. Although both have been thoroughly investigated, the “processes contributing to heterogeneity in the clinical manifestation of the disease remain unclear,” the researchers wrote.

Multiple studies show that each patient’s characteristics at disease onset — such as age, number of impaired functional domains (NIFDs; functions ranging from walking and balance, to problems with vision, fatigue, or limb numbness or pain), time to second relapse (TT2R), and early relapse activity (ERA) — can help to predict MS activity and progression. But factors are also likely to play a role in early disease presentation.

To pinpoint the mechanisms involved in disease variability and progression, researchers at Case Western Reserve University investigated the influence of those factors with known links to early disease presentation.

Their study analyzed data on 1,515 people in the Accelerated Cure Project Repository, an open-access resource containing clinical records from a U.S. population of MS patients. Machine learning and mathematical models were used to assess the relevance of each measure for each disease outcome.

Most patients were female (77.9%) and diagnosed with relapsing-remitting MS (RRMS). Their average age at onset was 33.4 years, and mean time to a second relapse was 3.6 years, the study found. Two was the median number for both problems in functional domains and relapses in the first two years.

Data revealed that genetic factors — including the presence of the HLA-DRB1*15:01 allele, an established genetic risk factor — and smoking were linked to earlier age at MS onset. In fact, the study found nearly half of patients of European ancestry were carriers of that gene variant, and 32.8% were recent smokers. Conversely, male patients and those who were obese, had lower education levels, or were diagnosed with primary progressive MS (PPMS) tended to be older at disease onset.

A greater degree of impairment in functional domains at onset was evident in those with RRMS and of lower socioeconomic status. Among RRMS patients, a shorter time to a second relapse (TT2R) was seen in people who were older at disease onset, obese, and with multiple lesions in the central nervous system. Younger and obese RRMS had greater evidence of early relapse activity (a higher ERA).

“Collectively, MS risk factors, including the genetic risk component, obesity, and smoking, (…) contribute independently to the heterogeneity in MS presentation and modulate early disease course evolution,” the researchers wrote.

“Noteworthy, are the effects (or lack thereof) of modifiable exposures (obesity and smoking) and the genetic susceptibility on the four outcomes [age of onset, NIFDs, TT2R, and ERA], which warrants future research aimed at improving prognostication of early disease activity (such as TT2R and ERA) as they may be indicative of long-term trajectories,” they concluded.