Vitamin D Levels May Modify Risk Genes for Macular Degeneration

By Joan Stephenson

September 08, 2015

NEW YORK (Reuters Health) - Vitamin D levels may substantially alter the odds of developing age-related macular degeneration (AMD) in women with certain gene variants associated with an elevated AMD risk, according to a new study.

The findings suggest that vitamin D deficiency "may increase one's risk for AMD, and that this increased risk may be greatest in those with the highest genetic risk for a specific variant in a protein called complement factor H (CFH)," lead author Dr. Amy Millen, of the University at Buffalo's School of Public Health and Health Professions, Buffalo, New York, told Reuters Health by email.

"We wanted to better understand if the association between vitamin D status and AMD was different in women with different genetic risk for AMD," Dr. Millen said.

To assess a potential interaction between vitamin D levels and genes associated with AMD risk, Dr. Millen and colleagues analyzed data from a subset of 913 women aged 54 to 74 for whom they had previously found an association between vitamin D status and AMD. The women are part of the Carotenoids in Age-Related Eye Disease Study (CAREDS).

Of the 913 women, "550 had adequate vitamin D levels (20 ng/mL or greater), 275 had inadequate levels (12 ng/mL up to 20 ng/mL), and 88 had deficient levels (less than 12 ng/mL)," the researchers reported online August 27 in JAMA Ophthalmology.

After adjusting for potentially confounding factors, women with deficient vitamin D status and two copies of the Y402 risk allele in CFH had 6.7-fold increased odds of AMD compared to the reference group (p=0.02), which for the joint analysis was noncarriers of risk alleles with a vitamin D status of 30 ng/mL or greater, presumed to be the lowest-risk group.

Vitamin D-deficient women with two copies of the high-risk complement factor I (CFI) allele (rs19933899) had a 6.3-fold increased odds of AMD (p=0.01).

The researchers saw a multiplicative interaction between vitamin D status and CFI, and additive interactions between vitamin D status and both CFH and CFI genotypes.

"These additive interactions suggest that the greatest burden (attributable risk) of AMD may be in vitamin D-deficient women with two high-risk alleles (CFH or CFI), indicating that the burden is above that expected from the addition of these two exposures alone," they wrote.

"This study is new in that it looks at the association of AMD with vitamin D levels (not intake) with respect to some of the known genetic risk factors for AMD," Dr. Michael B. Gorin, of the David Geffen School of Medicine, Los Angeles, who was not involved in the research, told Reuters Health by email. "The paper represents an incremental contribution to the field but strengthens the overall evidence that vitamin D levels are relevant."

The researchers say limitations of their study include the small sample size and the possibility that the findings might be due to chance or residual confounding.

"The numbers are relatively small and it is possible that other genetic variants failed to show an interaction or association because either the effects are weak or not detectable in this cohort," Dr. Gorin said. It is also possible, he noted, that some variants in genes such as ARMS2 might contribute so strongly to AMD that they would mask an interaction with vitamin D.

Dr. Millen said more work is needed to understand vitamin D's role in eye health. "These findings suggest that vitamin D may be another aspect of nutrition one needs to consider when thinking about eye health."


JAMA Ophthalmol 2015.


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