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The journal of nutrition, health & aging

, Volume 21, Issue 7, pp 772–780 | Cite as

Vitamin D status and prevalent early age-related macular degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study

  • Amy E. Millen
  • J. Nie
  • M. W. Sahli
  • J. A. Mares
  • K. J. Meyers
  • B. E. K. Klein
  • M. J. Lamonte
  • P. L. Lutsey
  • C. A. Andrews
  • R. Klein
Article

Abstract

Objectives

Vitamin D status has been hypothesized to protect against development of early age-related macular degeneration (AMD) via its anti-inflammatory properties and its possible beneficial influence on blood pressure control. We investigated the association between vitamin D status and prevalent early AMD in a community-based cohort.

Design

This was a cross-sectional study.

Setting

This was a secondary data analysis of already existing data from the Atherosclerosis Risk in Communities Study (ARIC) cohort collected from 1990 to 1995.

Participants

There were 9,734 (7,779 Caucasians, 1,955 African American) ARIC participants (aged 46 to 70 at visit 2 [1990-1992]) with 25(OH)D data available at visit 2, AMD assessment at visit 3 (1993-1995), and complete covariate data.

Measurements

Vitamin D status was assessed with serum 25-hydroxyvitamin D (25(OH)D) concentrations from bloods drawn at visit 2. Prevalent, early AMD (n=511) was assessed at visit 3 (1993-95) with nonmydriatic retinal photographs of one randomly chosen eye. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD by categories of 25(OH)D in nmol/L (deficient <30, inadequate 30-<50, and two categories of adequate status: 50-<75 and ≥75). Linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, and smoking status. We further adjusted for hypertension status to examine if vitamin D status influenced early AMD via its effects on blood pressure. Exploratory analyses of effect modification by age, sex, race and high risk genotypes [Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms] were conducted.

Results

The prevalence of early AMD was 5%, and 5% of participants were vitamin D deficient. The adjusted OR (95% CIs) for early AMD among those with adequate (=75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59-1.50), p-trend=0.86. Further adjustment for hypertension status did not influence results (OR [95% CI]=0.95 [0.59-1.52], p-trend=0.84). Results did not vary significantly by age, race, sex, early AMD subtype (soft drusen or retinal pigment epithelium depigmentation), or ARMS2 genotype. Results did not vary significantly by CFH genotype in African Americans. The p for multiplicative interaction between 25(OH)D and CFH genotype was 0.06 in Caucasians, but OR [95% CIs] for AMD by vitamin D status were similar in each CFH genotype and not statistically significant.

Conclusion

Vitamin D status was not associated with early AMD in this cohort sample.

Keywords

vitamin D 25-hydroxyvitamin D macular degeneration retinal diseases epidemiology cohort studies 

Supplementary material

12603_2016_827_MOESM1_ESM.doc (124 kb)
Supplementary material, approximately 123 KB.

References

  1. 1.
    Age-Related Eye Disease Study Research G. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of ophthalmology 2001;119(10):1417–36.CrossRefGoogle Scholar
  2. 2.
    Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Archives of ophthalmology 2007;125(5):661–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? The British journal of nutrition 2003;89(5):552–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nature reviews Immunology 2008;8(9):685–98. doi: 10.1038/nri2378.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kriegel MA, Manson JE, Costenbader KH. Does vitamin D affect risk of developing autoimmune disease?: a systematic review. Seminars in arthritis and rheumatism 2011;40(6):512–31 e8. doi: 10.1016/j.semarthrit.2010.07.009.CrossRefPubMedGoogle Scholar
  6. 6.
    Albert DM, Scheef EA, Wang S, Mehraein F, Darjatmoko SR, Sorenson CM, Sheibani N. Calcitriol is a potent inhibitor of retinal neovascularization. Invest Ophthalmol Vis Sci 2007;48(5):2327–34. doi: 10.1167/iovs.06-1210.CrossRefPubMedGoogle Scholar
  7. 7.
    Millen AE, Voland R, Sondel SA, Parekh N, Horst RL, Wallace RB, Hageman GS, Chappell R, Blodi BA, Klein ML, et al. Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women. Archives of ophthalmology 2011;129(4):481–9.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Graffe A, Milea D, Annweiler C, Beauchet O, Mauget-Faysse M, Beauchet O, Kodjikian L, Milea D. Association between hypovitaminosis D and late stages of age-related macular degeneration: a case-control study. Journal of the American Geriatrics Society 2012;60(7):1367–9. doi: 10.1111/j.1532-5415.2012.04015.x.CrossRefPubMedGoogle Scholar
  9. 9.
    Kim EC, Han K, Jee D. Inverse relationship between high blood 25-hydroxyvitamin D and late stage of age-related macular degeneration in a representative Korean population. Invest Ophthalmol Vis Sci 2014;55(8):4823–31. doi: 10.1167/iovs.14-14763.CrossRefPubMedGoogle Scholar
  10. 10.
    Itty S, Day S, Lyles KW, Stinnett SS, Vajzovic LM, Mruthyunjaya P. Vitamin D deficiency in neovascular versus nonneovascular age-related macular degeneration. Retina 2014;34(9):1779–86. doi: 10.1097/IAE.0000000000000178.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Singh A, Falk MK, Subhi Y, Sorensen TL. The association between plasma 25-hydroxyvitamin D and subgroups in age-related macular degeneration: a crosssectional study. PloS one 2013;8(7):e70948. doi: 10.1371/journal.pone.0070948.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Day S, Acquah K, Platt A, Lee PP, Mruthyunjaya P, Sloan FA. Association of vitamin D deficiency and age-related macular degeneration in medicare beneficiaries. Archives of ophthalmology 2012;130(8):1070–1. doi: 10.1001/archophthalmol.2012.439.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Golan S, Shalev V, Treister G, Chodick G, Loewenstein A. Reconsidering the connection between vitamin D levels and age-related macular degeneration. Eye 2011;25(9):1122–9. doi: 10.1038/eye.2011.174.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cougnard-Gregoire A, Merle BM, Korobelnik JF, Rougier MB, Delyfer MN, Feart C, Le Goff M, Dartigues JF, Barberger-Gateau P, Delcourt C. Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration. The Journal of nutrition 2015;145(8):1865–72. doi: 10.3945/jn.115.214387.CrossRefPubMedGoogle Scholar
  15. 15.
    Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. The Journal of nutrition 2012;142(3):498–507. doi: 10.3945/jn.111.151977.PubMedGoogle Scholar
  16. 16.
    IOM (Institute of Medicine). 2011. Summary. In: Dietary Reference Intakes for Calcium and Vitamin D. Washington DC: The National Academy Press: Page 1-14.Google Scholar
  17. 17.
    Barouch FC, Miller JW. The role of inflammation and infection in age-related macular degeneration. International ophthalmology clinics 2007;47(2):185–97. doi: 10.1097/IIO.0b013e3180377936.CrossRefPubMedGoogle Scholar
  18. 18.
    Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 2001;20(6):705–32.CrossRefPubMedGoogle Scholar
  19. 19.
    Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002;134(3):411–31.CrossRefPubMedGoogle Scholar
  20. 20.
    The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. American journal of epidemiology 1989;129(4):687–702.CrossRefGoogle Scholar
  21. 21.
    Millen AE, Meyers KJ, Liu Z, Engelman CD, Wallace RB, Le Blanc ES, Tinker LF, Iyengar SK, Robinson JG, Sarto GE, et al. Association between vitamin D status and age-related macular degeneration by genetic risk. JAMA Ophthalmol 2015;133(10):1171–9. doi: 10.1001/jamaophthalmol.2015.2715.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Baecke JA, Burema J, Frijters JE. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. The American journal of clinical nutrition 1982;36(5):936–42.PubMedGoogle Scholar
  23. 23.
    Pols MA, Peeters PH, Bueno- De-Mesquita HB, Ocke MC, Wentink CA, Kemper HC, Collette HJ. Validity and repeatability of a modified Baecke questionnaire on physical activity. International journal of epidemiology 1995;24(2):381–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Richardson MT, Ainsworth BE, Wu HC, Jacobs DR, Jr., Leon AS. Ability of the Atherosclerosis Risk in Communities (ARIC)/Baecke Questionnaire to assess leisuretime physical activity. International journal of epidemiology 1995;24(4):685–93.CrossRefPubMedGoogle Scholar
  25. 25.
    Klein R, Clegg L, Cooper LS, Hubbard LD, Klein BE, King WN, Folsom AR. Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study. Archives of ophthalmology 1999;117(9):1203–10.CrossRefPubMedGoogle Scholar
  26. 26.
    Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98(5 Suppl):786-806.Google Scholar
  27. 27.
    Folsom AR, Roetker NS, Rosamond WD, Heckbert SR, Basu S, Cushman M, Lutsey PL. Serum 25-hydroxyvitamin D and risk of venous thromboembolism: the Atherosclerosis Risk in Communities (ARIC) Study. Journal of thrombosis and haemostasis: JTH 2014;12(9):1455–60. doi: 10.1111/jth.12665.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Atherosclerosis Risk in Communities (ARIC) Study Research Group. Manual 8 Lipid and Lipoprotein Determinations. In. Chapell Hill, NC: Atherosclerosis Risk in Communities (ARIC) Study Research Group; 1991.Google Scholar
  29. 29.
    Holliday EG, Smith AV, Cornes BK, Buitendijk GH, Jensen RA, Sim X, Aspelund T, Aung T, Baird PN, Boerwinkle E, et al. Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study metaanalysis. PloS one 2013;8(1):e53830. doi: 10.1371/journal.pone.0053830.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Psaty BM, O’Donnell CJ, Gudnason V, Lunetta KL, Folsom AR, Rotter JI, Uitterlinden AG, Harris TB, Witteman JC, Boerwinkle E. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circulation 2009;2(1):73–80.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Feneis JF, Arora RR. Role of Vitamin D in Blood Pressure Homeostasis. American journal of therapeutics 2010.Google Scholar
  32. 32.
    Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. The Journal of steroid biochemistry and molecular biology 2004;89-90(1-5):387–92.CrossRefPubMedGoogle Scholar
  33. 33.
    Seddon JM, Reynolds R, Shah HR, Rosner B. Smoking, Dietary Betaine, Methionine, and Vitamin D in Monozygotic Twins with Discordant Macular Degeneration: Epigenetic Implications. Ophthalmology 2011 May 25. [Epub ahead of print].Google Scholar
  34. 34.
    Morrison MA, Silveira AC, Huynh N, Jun G, Smith SE, Zacharaki F, Sato H, Loomis S, Andreoli MT, Adams SM, et al. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration. Human genomics 2011;5(6):538–68.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the Age-Related Eye Disease Study Report Number 6. Am J Ophthalmol 2001;132(5):668–81.CrossRefGoogle Scholar
  36. 36.
    Meleth, A.D., Raiji V.R., Krishnadev N., and Chew E (2011). Therapy of Nonexudative Age-Related Macular Degeneration In Ho, A.C. and Regillo C.D. (Eds.), Age-related Macular Degeneration Diagnosis and Treatment (pp. 65-78). New York, NY: Springer New York.Google Scholar
  37. 37.
    Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Journal of the National Cancer Institute 2006;98(7):451–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Millen AE, Wactawski-Wende J, Pettinger M, Melamed ML, Tylavsky FA, Liu S, Robbins J, LaCroix AZ, LeBoff MS, Jackson RD. Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: the Women’s Health Initiative Calcium plus Vitamin D clinical trial. The American journal of clinical nutrition 2010;91(5):1324–35.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Hofmann JN, Yu K, Horst RL, Hayes RB, Purdue MP. Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev 2010;19(4):927–31. doi: 10.1158/1055-9965.EPI-09-1121.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. American journal of epidemiology 2010;171(8):903–8. doi: 10.1093/aje/kwq005.CrossRefPubMedGoogle Scholar
  41. 41.
    Meng JE, Hovey KM, Wactawski-Wende J, Andrews CA, Lamonte MJ, Horst RL, Genco RJ, Millen AE. Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women. Cancer Epidemiol Biomarkers Prev 2012;21(6):916–24. doi: 10.1158/1055-9965.EPI-12-0026.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Atherosclerosis Risk in Communities Study. Exam 2. Derived Variable Dictionary. Version 2.10. June 2010. https://www2.cscc.unc.edu/aric/sites/default/files/public/manuals/DERIVE2_10.pdf (Accessed July 28, 2016).Google Scholar

Copyright information

© Serdi and Springer-Verlag France 2017

Authors and Affiliations

  • Amy E. Millen
    • 1
  • J. Nie
    • 1
  • M. W. Sahli
    • 2
  • J. A. Mares
    • 3
  • K. J. Meyers
    • 3
  • B. E. K. Klein
    • 3
  • M. J. Lamonte
    • 1
  • P. L. Lutsey
    • 4
  • C. A. Andrews
    • 5
  • R. Klein
    • 3
  1. 1.Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at BuffaloThe State University of New YorkBuffaloUSA
  2. 2.Department of Public Health and Health Sciences, School of Health Professions and StudiesUniversity of Michigan-FlintFlintUSA
  3. 3.Department of Ophthalmology and Visual Sciences, School of Medicine and Public HealthThe University of Wisconsin-MadisonMadisonUSA
  4. 4.Division of Epidemiology and Community Health, School of Public HealthUniversity of MinnesotaMinneapolisUSA
  5. 5.Department of Ophthalmology and Visual SciencesUniversity of Michigan Medical SchoolAnn ArborUSA

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