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BALTIMORE—A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detects patients with multiple sclerosis (MS) who have an increased risk for relapse, according to a multicenter cohort study. The findings could have clinical significance in MS treatment and patient counseling, said Jennifer S. Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco, at the 141st Annual Meeting of the American Neurological Association.

Low vitamin D levels are associated with an increased risk of MS, but whether this association is causal has not been determined. Dr. Graves and her colleagues sought to gain insight into the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that previously had been discovered to be involved in the manufacture of 25-OH vitamin D. The investigators analyzed the relationship of these SNPs to relapses in patients with MS.

Jennifer S. Graves, MD, PhD

They compared the SNP profiles of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) with those of a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level. Patients in the discovery cohort were enrolled at two pediatric MS centers in California between 2006 and 2011, and those in the replication cohort were enrolled at nine MS centers in the United States from 2011 to 2015.

Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. The lowest and highest risk scores had linear associations with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in the discovery and replication cohorts. The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score.

“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.

The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.

The study was funded by the Race to Erase MS, the National MS Society, and the National Institute of Neurological Disorders and Stroke.

Brian Hoyle

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BALTIMORE—A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detects patients with multiple sclerosis (MS) who have an increased risk for relapse, according to a multicenter cohort study. The findings could have clinical significance in MS treatment and patient counseling, said Jennifer S. Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco, at the 141st Annual Meeting of the American Neurological Association.

Low vitamin D levels are associated with an increased risk of MS, but whether this association is causal has not been determined. Dr. Graves and her colleagues sought to gain insight into the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that previously had been discovered to be involved in the manufacture of 25-OH vitamin D. The investigators analyzed the relationship of these SNPs to relapses in patients with MS.

Jennifer S. Graves, MD, PhD

They compared the SNP profiles of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) with those of a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level. Patients in the discovery cohort were enrolled at two pediatric MS centers in California between 2006 and 2011, and those in the replication cohort were enrolled at nine MS centers in the United States from 2011 to 2015.

Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. The lowest and highest risk scores had linear associations with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in the discovery and replication cohorts. The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score.

“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.

The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.

The study was funded by the Race to Erase MS, the National MS Society, and the National Institute of Neurological Disorders and Stroke.

Brian Hoyle

BALTIMORE—A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detects patients with multiple sclerosis (MS) who have an increased risk for relapse, according to a multicenter cohort study. The findings could have clinical significance in MS treatment and patient counseling, said Jennifer S. Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco, at the 141st Annual Meeting of the American Neurological Association.

Low vitamin D levels are associated with an increased risk of MS, but whether this association is causal has not been determined. Dr. Graves and her colleagues sought to gain insight into the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that previously had been discovered to be involved in the manufacture of 25-OH vitamin D. The investigators analyzed the relationship of these SNPs to relapses in patients with MS.

Jennifer S. Graves, MD, PhD

They compared the SNP profiles of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) with those of a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level. Patients in the discovery cohort were enrolled at two pediatric MS centers in California between 2006 and 2011, and those in the replication cohort were enrolled at nine MS centers in the United States from 2011 to 2015.

Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. The lowest and highest risk scores had linear associations with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in the discovery and replication cohorts. The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score.

“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.

The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.

The study was funded by the Race to Erase MS, the National MS Society, and the National Institute of Neurological Disorders and Stroke.

Brian Hoyle

Issue
Neurology Reviews - 24(11)
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Page Number
42
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42
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