2 Genes make AMD 6X more likely if low vitamin D - Aug 2015

Association Between Vitamin D Status and Age-Related Macular Degeneration by Genetic Risk.

JAMA Ophthalmol. 2015 Aug 27. doi: 10.1001/jamaophthalmol.2015.2715. [Epub ahead of print]
Millen AE1, Meyers KJ2, Liu Z2, Engelman CD3, Wallace RB4, LeBlanc ES5, Tinker LF6, Iyengar SK7, Robinson JG8, Sarto GE9, Mares JA2.
1Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo.
2Department of Ophthalmology and Visual Sciences, The University of Wisconsin, Madison.
3Department of Population Health Sciences, The University of Wisconsin, Madison.
4Department of Epidemiology, The University of Iowa, Iowa City.
5The Center for Health Research, Kaiser Permanente Research, Portland, Oregon.
6Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
7Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
8Department of Epidemiology, University of Iowa College of Public Health, Iowa City.
9Department of Obstetrics and Gynecology, School of Medicine & Public Health, University of Wisconsin, Madison.

IMPORTANCE:
Deficient 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with increased odds of age-related macular degeneration (AMD).

OBJECTIVE:
To examine whether this association is modified by genetic risk for AMD and whether there is an association between AMD and single-nucleotide polymorphisms of genes involved in vitamin D transport, metabolism, and genomic function.

DESIGN, SETTING, AND PARTICIPANTS:
Postmenopausal women (N = 913) who were participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS) (aged 54 to <75 years) with available serum 25(OH)D concentrations (assessed October 1, 1993, to December 31, 1998), genetic data, and measures of AMD (n = 142) assessed at CAREDS baseline from May 14, 2001, through January 31, 2004, were studied.

MAIN OUTCOMES AND MEASURES:
Prevalent early or late AMD was determined from graded, stereoscopic fundus photographs. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for AMD by the joint effects of 25(OH)D (<12, ≥12 to <20, ≥20 to <30, and ≥30 ng/mL) and risk genotype (noncarrier, 1 risk allele, or 2 risk alleles). The referent group was noncarriers with adequate vitamin D status (≥30 ng/mL). Joint effect ORs were adjusted for age, smoking, iris pigmentation, self-reported cardiovascular disease, self-reported diabetes status, and hormone use. Additive and multiplicative interactions were assessed using the synergy index (SI) and an interaction term, respectively. To examine the association between AMD and variants in vitamin D-related genes, age-adjusted ORs and 95% CIs were estimated using logistic regression.

RESULTS:
Among the 913 women, 550 had adequate levels of vitamin D (≥20 ng/mL), 275 had inadequate levels (≥12 to <20 mg/mL), and 88 had deficient levels (<12 ng/mL). A 6.7-fold increased odds of AMD (95% CI, 1.6-28.2) was observed among women with deficient vitamin D status (25[OH]D <12 ng/mL) and 2 risk alleles for CFH Y402H (SI for additive interaction, 1.4; 95% CI, 1.1-1.7; P for multiplicative interaction = .25). Significant additive (SI, 1.4; 95% CI, 1.1-1.7) and multiplicative interactions (P = .02) were observed for deficient women with 2 high-risk CFI (rs10033900) alleles (OR, 6.3; 95% CI, 1.6-24.2). The odds of AMD did not differ by genotype of candidate vitamin D genes.

CONCLUSIONS AND RELEVANCE:
In this study, the odds of AMD were highest in those with deficient vitamin D status and 2 risk alleles for the CFH and CFI genotypes, suggesting a synergistic effect between vitamin D status and complement cascade protein function. Limited sample size led to wide CIs. Findings may be due to chance or explained by residual confounding.

PMID: 26312598

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Vitamin D may play key role in preventing macular degeneration
Science Daily report of this study
""Our message is not that achieving really high levels of vitamin D are good for the eye, but that having deficient vitamin D levels may be unhealthy for your eyes," Millen says."

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Comment by VitaminDWiki
Suspect that the un-named genes reduced the bio-available vitamin D as well as the measured vitamin D

See also VitaminDWiki

• Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
• Hip Fracture 2.5 times more likely if poor Vitamin D Binding Protein gene - Aug 2015
• Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014 GC
• Male late stage Age-Related Macular Degeneration is strongly associated with low vitamin D – July 2014
• Macular degeneration 4X more likely if low vitamin D and a particular gene – May 2013 CFH Y402H polymorphism
• Macular Degeneration decreased with UV and perhaps Vitamin D genetics– Oct 2011
• Search vitaminDWiki for "macular degeneration" OR AMD 232 items as of Nov 2015
• Late stage AMD 2.2 more likely if low vitamin D – meta-analysis April 2016

The items in both Vision and Genetics: