Variations in Biological Clock Genes May Increase Risk of MS, Study Reports

Researchers have found a link between variations in two genes that control our 24-hour biological clock and the risk of a person developing multiple sclerosis.

The study, “Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis,” was published in the journal PLOS ONE.

Scientists know MS is less prevalent closer to the equator, such as in South America, Asia and sub-Saharan Africa, than in regions far to the north or south of it. The far-flung areas include Canada, the northern United States, northern Europe, and southern Australia.

The reasons behind this geographical association are unclear, although scientists know that low vitamin D levels, which stem from less sunshine, are a risk factor for MS.

A team of researchers wondered if different geographical locations, with their light and temperature differences, could influence the risk of MS by affecting our biological clock.

This clock, which scientists call our circadian rhythm, is a crucial part of our physiology. It controls our  sleeping and waking patterns, for example. And light and temperature play a major role in it.

Scientists say the clock runs our brain and organs, adjusting our hormones, behavior, cognition, metabolism and immune system to the time of day.

One measure of the circadian rhythm’s importance is that it exists not only in humans but in many living things.

When the circadian rhythm is disturbed — for instance, when a person works a night shift — it can increase the risk of a health disorder. In fact, the risk of MS is higher among people working shifts, especially if they started when they were younger than 20 years old, research indicates.

And a recent study demonstrated that disrupting the circadian rhythm of a mouse model of MS led to a more severe progression of the disease.

Researchers decided to explore the link between circadian rhythm and MS at the genetic level. They looked for variations in genes at the core of our circadian clock.

The study included 900 MS patients and 1,024 healthy controls, all of Slavic origin — Slovenians, Croatians, and Serbs. The team analyzed DNA extracted from their blood for variations in the biological clock genes CLOCK and ARNTL.

They discovered that the rs3789327 variation in the CLOCK gene and the rs6811520 variation in the ARNTL gene significantly increased the risk of women developing MS, although it had no correlation with men.

In addition, the association between the ARNTL variation and risk applied only to patients with relapsing-remitting MS, and not with other types.

Taken together, the results pointed to a link between disturbances in circadian rhythm and development of MS.

The team said disrupting the circadian rhythm may alter “daily cellular molecular metabolic mechanisms and therefore contribute to neurodegeneration on a long-term basis.”

“Since cellular metabolic mechanisms are related not specifically to neurodegeneration but to all states of health and disease, circadian rhythms are an important mechanism to be studied in chronic diseases,” they concluded.