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Chitra K. Karki, Sudha K. Iyengar, Barbara Truitt, Robert P. Igo, Jr., Elizabeth Johnson, Lesley Tinker, Kristin J. Meyers, Julie A. Mares; Genetic Determinants of Serum Lutein and Zeaxanthin Levels in the Carotenoids in Age-Related Eye Diseases Study. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5642.
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To investigate genetic determinants of serum lutein and zeaxanthin levels in women of the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study to the Women’s Health Initiative Observational Study (WHI-OS).
The sample consists of 1,697 post-menopausal women (ages 50-79 years) selected from the Iowa, Wisconsin, and Oregon cohorts of the WHI, whose serum lutein and zeaxanthin levels have been estimated from samples collected at the WHI baseline (1994-1998). Dietary intake of lutein and zeaxanthin was estimated using a food frequency questionnaire. Blood samples were genotyped for 320 single nucleotide polymorphisms (SNPs) in 14 candidate genes related to absorption, transport, binding, and cleavage of carotenoids or transport of lipids. SNPs were individually tested for associations with serum lutein and zeaxanthin using least-squares linear regression assuming an additive genetic model and adjusting for age, ancestry via principal components, and dietary intake of lutein and zeaxanthin.
SNPs from ten genes were significantly associated with serum levels of lutein and zeaxanthin. The strongest relationship was for rs11645428 (βA=0.049, P=1.50x10-21) in BCMO1, a pro-vitamin A carotenoid cleavage enzyme related to serum response to dietary carotenoid. The minor allele, A (frequency=34%) conferred higher levels of lutein and zeaxanthin: mean serum trans lutein and zeaxanthin (µmol/L) (standard deviation) for individuals homozygous GG was 0.28 (0.14), heterozygous 0.33 (0.15) and homozygous AA was 0.36 (0.18). Also significant were rs10846744 (βC=0.024, P=6.3x10-4) in SCARB1, which codes for a plasma membrane scavenger lipoprotein receptor related to carotenoid uptake and rs9892427 (βG= -0.028, P=0.0016) in STARD3, a lipid trafficking protein related to exporting cholesterol, which also binds lutein in the retina.
Independent of dietary intake of lutein and zeaxanthin, genetic variation in candidate genes related to uptake and metabolism of carotenoids are predictors of serum levels of lutein and zeaxanthin in postmenopausal women. Further research into genetic associations with carotenoid metabolism, transport and accumulation in the retina is underway and may provide insight into the complex interplay between genetics and carotenoid intake in relation to risk for maculopathy.
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