Author Topic: Genetics may give clue to MS connection with vitamin D  (Read 41 times)

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Offline agate

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Genetics may give clue to MS connection with vitamin D
« on: October 19, 2016, 02:53:17 pm »
From MedPage Today, October 19, 2016:

ANA: Genetics May Solve Puzzle of MS and Vitamin D

Polymorphisms in pediatric MS patients indicate higher relapse likelihood

by Ed Susman
Contributing Writer, MedPage Today

BALTIMORE -- Pediatric multiple sclerosis patients with a genetic predisposition to low vitamin D levels were at a higher risk for relapses, researchers reported here.

Six units of the Vitamin D Genetic Risk Score based on analyses of single nucleotide polymorphisms (SNPs) was associated with a 94% increase in the hazard of relapse [HR 1.94 (95% CI 1.19-3.15, P=0.0007)] in a group of children and adolescents with MS, said Jennifer Graves, MD, of the University of California San Francisco.

"A risk score of three of these SNPs with independent effects was normally distributed and explained 13% of the variance of vitamin D level in these subjects," Graves told MedPage Today at her poster presentation during the annual meeting of the American Neurological Association.

"These findings support a causal association of vitamin D with relapse rate," she said.

"Six units of the Vitamin D Genetic Risk Score, comparing highest to lowest scores, was associated with 14.9 ng/mL lower vitamin D level (P=0.0000052)," she said. "This is quite remarkable. Even in a sample size of 181 children we have reached almost genome level significance.

"The effect size was nearly identical in a 110-patient replication cohort that did not include any of the children in the 181-patient discovery set," Graves said.

Graves and colleagues developed the Genetic Risk Score by assigning values to the SNPs that in the literature are associated with vitamin D levels. The three independent SNP alleles were identified as rs7041, rs909217 and rs2276360.

"Our project was to look at the genetic drivers of vitamin D levels the polymorphisms that are associated with serum vitamin D levels," Graves explained. "These are things that you are born with; that's the card that you are dealt."
She said a lot of discussion about vitamin D revolves around whether levels are low because a person with multiple sclerosis doesn't get in the sun enough due to the weight of disability. She said her look at the genetic underpinnings of vitamin D levels "hopefully puts you upstream of confounding factors."

To create the vitamin D genetic risk score, the research team examined DNA samples from 181 pediatric multiple sclerosis patients typed for 29 functional polymorphisms in vitamin D pathway genes, identified through the literature to be associated with 25-hydroxyvitamin D (25-OH-D) levels in human subjects. Through regression modeling, the researchers determined that six of the SNPs were strongly associated with vitamin D levels in the pediatric multiple sclerosis patients.
Graves said that the researchers are continuing to determine if the association with relapses can be confirmed, pending accumulation of additional patients and follow-up time in the second cohort.

The results of Graves' study does not reveal if supplementation with vitamin D in the patients with a high genetic risk score will reduce relapses. However, in ongoing studies with vitamin D, she said that DNA material is being collected to help scientists find the answer to that question of how the patients respond to therapy based on their genotype.

The patients in the discovery set were about 13 years old and 66% were girls. The median follow-up was about 34 months, and the patients averaged about one relapse a year. About 65% of the cohort were white; another 30% of the patients were Hispanic. Their baseline median 25-OH-D level was 23 ng/mL.

In commenting on the study, Dhanashri Miskin, MD, of Lenox Hill Hospital, New York City, told MedPage Today, "This research is very interesting as the authors seek to identify a genetic cause for low 25-OH-D levels in multiple sclerosis patients.

"However, I don't know how practical it is to [do] this test, which is most likely not commercially available and expensive, on every MS patient. The more practical approach is to screen all MS patients for 25-OH vitamin D deficiency and optimize their level with vitamin D supplementation with a goal of a least 50 ng/mL.

"I think more research needs to be done to determine a causal association of vitamin D level and relapse rate," Miskin said.

Graves disclosed relevant relationships with Biogen and Genentech.

Miskin disclosed no relevant relationships with industry.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.


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