TY - JOUR
T1 - Evaluation of new and established age-related macular degeneration susceptibility genes in the Women'S Health Initiative Sight Exam (WHI-SE) study
AU - Peter, Inga
AU - Huggins, Gordon S.
AU - Ordovas, Jose M.
AU - Haan, Mary
AU - Seddon, Johanna M.
N1 - Funding Information:
All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Publication of this article was supported by the Russo Dual-Investigator Grant, Tufts University School of Medicine, Boston, Massachusetts; Grant RO1-EY11309 from the National Institutes of Health , Bethesda, Maryland; Massachusetts Lions Eye Research Fund, Inc, New Bedford, Massachusetts; Research to Prevent Blindness, Inc, New York, New York; and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. WHI-SE was funded by Wyeth-Ayerst Laboratories, Inc, Collegeville, Pennsylvania; and WHI was funded by National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Tufts Medical Center has filed a patent application for some materials related to this work. Involved in design and conduct of the study (I.P., M.H., J.M.S.); collection and interpretation of the data (I.P., G.S.H., J.M.O., M.H., J.M.S.); and preparation, review, or approval of the manuscript (I.P., G.S.H., J.M.O., M.H., J.M.S.). This ancillary study was approved by the Institutional Review Board of Tufts University School of Medicine and Tufts Medical Center and the WHI ancillary study subcommittee.
PY - 2011/12
Y1 - 2011/12
N2 - Purpose: To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. Design: Multicenter case-control study. Methods: One hundred and forty-six women with intermediate and late stages of AMD and 1269 subjects without AMD underwent ocular examinations and fundus photography to determine stage of AMD. Fourteen polymorphisms at or near 11 genes, including previously confirmed genes CFH, ARMS2/HTRA1, C2, C3, and CFI; recently reported AMD genes in the high-density lipoprotein cholesterol (HDL) pathway LIPC, ABCA1, CETP, and LPL; TIMP3/SYN3, a known ocular gene recently linked with AMD; and APOE, were assessed using logistic regression analysis. Results: After adjustment for demographic, behavioral, and other genetic factors, a protective effect was detected among TT carriers compared with non-carriers for the HDL pathway gene, LIPC rs493258, for intermediate and late AMD (OR [95% confidence interval]: 0.3 [0.20.7], P =.003). Variants in CFH rs1410996, ARMS2/HTRA1 A69S, and C3 R102G were significantly associated with an increased risk of AMD. Individuals with the homozygous CFI rs10033900 TT genotype had a 2.9 [1.27.2]-fold increased risk, and those with the CFH Y402H GG genotype had a 2.2 [1.04.8]-fold higher risk of developing AMD compared with non-carriers. APOE4 carriers may have a reduced risk of intermediate/late AMD (OR = 0.5 [0.30.9], P =.015. Suggestive associations were seen between AMD and the HDL pathway genes CETP and LPL. Conclusion: In this unique national cohort of women, we found associations with established AMD-related genetic factors and the recently reported LIPC gene in the HDL pathway. These findings may help develop novel therapeutic targets to treat or delay the onset of the disease.
AB - Purpose: To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. Design: Multicenter case-control study. Methods: One hundred and forty-six women with intermediate and late stages of AMD and 1269 subjects without AMD underwent ocular examinations and fundus photography to determine stage of AMD. Fourteen polymorphisms at or near 11 genes, including previously confirmed genes CFH, ARMS2/HTRA1, C2, C3, and CFI; recently reported AMD genes in the high-density lipoprotein cholesterol (HDL) pathway LIPC, ABCA1, CETP, and LPL; TIMP3/SYN3, a known ocular gene recently linked with AMD; and APOE, were assessed using logistic regression analysis. Results: After adjustment for demographic, behavioral, and other genetic factors, a protective effect was detected among TT carriers compared with non-carriers for the HDL pathway gene, LIPC rs493258, for intermediate and late AMD (OR [95% confidence interval]: 0.3 [0.20.7], P =.003). Variants in CFH rs1410996, ARMS2/HTRA1 A69S, and C3 R102G were significantly associated with an increased risk of AMD. Individuals with the homozygous CFI rs10033900 TT genotype had a 2.9 [1.27.2]-fold increased risk, and those with the CFH Y402H GG genotype had a 2.2 [1.04.8]-fold higher risk of developing AMD compared with non-carriers. APOE4 carriers may have a reduced risk of intermediate/late AMD (OR = 0.5 [0.30.9], P =.015. Suggestive associations were seen between AMD and the HDL pathway genes CETP and LPL. Conclusion: In this unique national cohort of women, we found associations with established AMD-related genetic factors and the recently reported LIPC gene in the HDL pathway. These findings may help develop novel therapeutic targets to treat or delay the onset of the disease.
UR - http://www.scopus.com/inward/record.url?scp=81855198945&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2011.05.016
DO - 10.1016/j.ajo.2011.05.016
M3 - Article
AN - SCOPUS:81855198945
SN - 0002-9394
VL - 152
SP - 1005-1013.e1
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
IS - 6
ER -