TY - JOUR
T1 - Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration
AU - Cao, Sijia
AU - Ko, Ashley
AU - Partanen, Marita
AU - Pakzad-Vaezi, Kaivon
AU - Merkur, Andrew B.
AU - Albiani, David A.
AU - Kirker, Andrew W.
AU - Wang, Aikun
AU - Cui, Jing Z.
AU - Forooghian, Farzin
AU - Matsubara, Joanne A.
N1 - Funding Information:
All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest and none were reported. This research was supported by a New Researcher Grant from the Canadian National Institute for the Blind , Toronto, ON, Canada, and by Grant CIHR MOP 97806 from the Canadian Institute of Health Research , Ottawa, ON, Canada. Involved in Concept and design of study (A.K., F.F., J.A.M., S.C.); Recruitment of patients (A.B.M., D.A.A., A.W.K.); Conduct of study (A.K., A.W., J.Z.C., K.P.-V., S.C.); Analysis and interpretation of data (A.W., J.A.M., M.P., S.C.); Statistical expertise (M.P.); Obtaining funding (F.F., J.A.M.); Writing article (J.A.M., S.C.); Critical revision of article (A.K., F.F., J.Z.C., M.P.); and Final approval of article (J.A.M., F.F.). The authors thank Carl Zeiss Meditec, Inc, for use of the Cirrus SD OCT machine and software.
PY - 2013/12
Y1 - 2013/12
N2 - Purpose To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD). Design Cross-sectional study. Methods Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons. Results The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P <.01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor α than those with the CT variants, the TT variant, or both (P <.01). Interleukin-1β did not reach significance (P =.02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P >.15). Conclusions The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology.
AB - Purpose To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD). Design Cross-sectional study. Methods Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons. Results The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P <.01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor α than those with the CT variants, the TT variant, or both (P <.01). Interleukin-1β did not reach significance (P =.02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P >.15). Conclusions The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology.
UR - http://www.scopus.com/inward/record.url?scp=84888014482&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2013.08.003
DO - 10.1016/j.ajo.2013.08.003
M3 - Article
C2 - 24083687
SN - 0002-9394
VL - 156
SP - 1176
EP - 1183
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
IS - 6
ER -