Genetic risk score for low vitamin D may affect MS relapse rate

 

BALTIMORE – A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detected multiple sclerosis patients with an increased risk for relapse in a multicenter cohort study.

The findings could have clinical significance in multiple sclerosis (MS) treatment and patient counseling, Jennifer S. Graves, MD, PhD, of the University of California, San Francisco, said in a brief oral and poster presentation of the study at the 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 potential causality of vitamin D in the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that had been previously been discovered to be involved in the manufacture of 25-OH vitamin D and finding their relationship to relapse in patients with MS.

The investigators compared the SNP profile of a discovery cohort of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) who were enrolled at two pediatric MS centers in California between 2006 and 2011 against a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level who were enrolled at nine MS centers elsewhere 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. A comparison of the lowest and highest scores revealed a linear association with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in both the discovery and replication cohorts (P = .00000052 and .002, respectively).

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 (hazard ratio, 1.94; 95% confidence interval, 1.19-3.15; P = .007).

“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 Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.

 

BALTIMORE – A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detected multiple sclerosis patients with an increased risk for relapse in a multicenter cohort study.

The findings could have clinical significance in multiple sclerosis (MS) treatment and patient counseling, Jennifer S. Graves, MD, PhD, of the University of California, San Francisco, said in a brief oral and poster presentation of the study at the 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 potential causality of vitamin D in the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that had been previously been discovered to be involved in the manufacture of 25-OH vitamin D and finding their relationship to relapse in patients with MS.

The investigators compared the SNP profile of a discovery cohort of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) who were enrolled at two pediatric MS centers in California between 2006 and 2011 against a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level who were enrolled at nine MS centers elsewhere 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. A comparison of the lowest and highest scores revealed a linear association with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in both the discovery and replication cohorts (P = .00000052 and .002, respectively).

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 (hazard ratio, 1.94; 95% confidence interval, 1.19-3.15; P = .007).

“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 Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.

 

BALTIMORE – A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detected multiple sclerosis patients with an increased risk for relapse in a multicenter cohort study.

The findings could have clinical significance in multiple sclerosis (MS) treatment and patient counseling, Jennifer S. Graves, MD, PhD, of the University of California, San Francisco, said in a brief oral and poster presentation of the study at the 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 potential causality of vitamin D in the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that had been previously been discovered to be involved in the manufacture of 25-OH vitamin D and finding their relationship to relapse in patients with MS.

The investigators compared the SNP profile of a discovery cohort of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) who were enrolled at two pediatric MS centers in California between 2006 and 2011 against a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level who were enrolled at nine MS centers elsewhere 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. A comparison of the lowest and highest scores revealed a linear association with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in both the discovery and replication cohorts (P = .00000052 and .002, respectively).

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 (hazard ratio, 1.94; 95% confidence interval, 1.19-3.15; P = .007).

“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 Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.