Multiple Sclerosis in genetically susceptible twins is augmented by the northern environment

A new study of twins suggests that living farther north of the equator significantly increases risk of developing Multiple Sclerosis (MS) among those with genetic susceptibility due to some environmental factor.

By following more than 700 pairs of twins diagnosed with MS, researchers from the Keck School of Medicine of the University of Southern California found that people born in the north tended to come to physicians for diagnosis slightly earlier than those born farther south, and that the tendency for identical twins to both be diagnosed was greater in those born in the north.

The concordance (both twins being diagnosed with MS) among identical twin pairs born in the north was nearly twice as high as among those born elsewhere (18.6 % vs. 9.5%). There was significantly less concordance among fraternal twins. The results were published in the in the July issue of Annals of Neurology.

Locations categorized as "northern" included Canada or states at or above 42 degrees north, including Alaska, Oregon, Washington, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Michigan, Minnesota, Wisconsin, Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island and Vermont.

Twins were divided into two categories, either monozygotic (identical twins with the same genetic makeup, coming from one egg) or dizygotic (fraternal twins, coming from two separate eggs). An effect that is seen more commonly in the monozygotic twins suggests a heavier role is being played by genes.

"We've known that MS is more common the farther away from the equator you get," says Thomas Mack, professor of preventive medicine at the Keck School of Medicine of USC and lead author of the study. "By looking at the number of times this occurs in twins both identical and fraternal twins we could see whether it was just a matter of latitude or if there is something else. This study suggests there's more concordance among identical twins, which means there is some environmental exposure and it is interacting with the genes."

If environment alone was responsible for the increased incidence of both members of the twin pair getting MS, there would be similarly high concordance among fraternal twins. The study did not suggest that, however, showing instead that both identical twins were far more likely to get the disease than both fraternal twins.

In fact, despite clear evidence of a much higher incidence of MS among women, the study found high concordance in both male and female identical twins, implying that mechanisms of inheritance are probably identical by sex. In other words, genetic susceptibility trumps the traditional bias against MS in most males.

Northern residence also contributed significantly to earlier onset of the disease. The researchers suggest that an early onset in the North could represent an early environmental deficit in protection, such as by less opportunity for early exposure to the sun, or for unknown reasons to an unrecognized causal factor, such as a virus. "It may even be that exposure to the sun interrupts whatever effect a virus has," Mack says.

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The study was supported by the Multiple Sclerosis Society, the National Institute of Neurological Disease and Stroke (a part of the NIH), and the National Cancer Institute.

Talat Islam, W. James Gauderman, Wendy Cozen, Ann S. Hamilton, Margaret E. Burnett and Thomas M. Mack, "Differential Twin Concordance for Multiple Sclerosis by Latitude of Birthplace." Annals of Neurology Volume 60, Issue 1, Date: July 2006, Pages: 56-64


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