Inflammation, Complement Factor H, and Age-Related Macular Degeneration. The Multi-Ethnic Study of Atherosclerosis

Ronald Klein, Michael D. Knudtson, Barbara E K Klein, Tien Y. Wong, Mary Frances Cotch, Kiang Liu, Ching Y. Cheng, Gregory L. Burke, Mohammed F. Saad, David R. Jacobs, A. Richey Sharrett

Research output: Contribution to journalArticle

Abstract

Objective: To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Design: Population-based, cross-sectional study. Participants: We included 5887 persons aged 45 to 84 years with gradable AMD. Methods: Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Main Outcome Measure: Prevalence of AMD. Results: While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14-2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06-1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14-3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10-2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09-3.10), and large drusen area (OR, 1.66; 95% CI, 1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. Conclusions: This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Original languageEnglish (US)
Pages (from-to)1742-1749
Number of pages8
JournalOphthalmology
Volume115
Issue number10
DOIs
StatePublished - Oct 2008

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Complement Factor H
Macular Degeneration
Atherosclerosis
Inflammation
Odds Ratio
Confidence Intervals
Hispanic Americans
Genotype
Geographic Atrophy
Population
Retinal Pigments
Cyclooxygenase 2 Inhibitors
Population Growth
Disclosure
Periodontal Diseases
Ethnic Groups
C-Reactive Protein
Arthritis
Interleukin-6
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Klein, R., Knudtson, M. D., Klein, B. E. K., Wong, T. Y., Cotch, M. F., Liu, K., ... Sharrett, A. R. (2008). Inflammation, Complement Factor H, and Age-Related Macular Degeneration. The Multi-Ethnic Study of Atherosclerosis. Ophthalmology, 115(10), 1742-1749. https://doi.org/10.1016/j.ophtha.2008.03.021

Inflammation, Complement Factor H, and Age-Related Macular Degeneration. The Multi-Ethnic Study of Atherosclerosis. / Klein, Ronald; Knudtson, Michael D.; Klein, Barbara E K; Wong, Tien Y.; Cotch, Mary Frances; Liu, Kiang; Cheng, Ching Y.; Burke, Gregory L.; Saad, Mohammed F.; Jacobs, David R.; Sharrett, A. Richey.

In: Ophthalmology, Vol. 115, No. 10, 10.2008, p. 1742-1749.

Research output: Contribution to journalArticle

Klein, R, Knudtson, MD, Klein, BEK, Wong, TY, Cotch, MF, Liu, K, Cheng, CY, Burke, GL, Saad, MF, Jacobs, DR & Sharrett, AR 2008, 'Inflammation, Complement Factor H, and Age-Related Macular Degeneration. The Multi-Ethnic Study of Atherosclerosis', Ophthalmology, vol. 115, no. 10, pp. 1742-1749. https://doi.org/10.1016/j.ophtha.2008.03.021
Klein, Ronald ; Knudtson, Michael D. ; Klein, Barbara E K ; Wong, Tien Y. ; Cotch, Mary Frances ; Liu, Kiang ; Cheng, Ching Y. ; Burke, Gregory L. ; Saad, Mohammed F. ; Jacobs, David R. ; Sharrett, A. Richey. / Inflammation, Complement Factor H, and Age-Related Macular Degeneration. The Multi-Ethnic Study of Atherosclerosis. In: Ophthalmology. 2008 ; Vol. 115, No. 10. pp. 1742-1749.
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abstract = "Objective: To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Design: Population-based, cross-sectional study. Participants: We included 5887 persons aged 45 to 84 years with gradable AMD. Methods: Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Main Outcome Measure: Prevalence of AMD. Results: While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95{\%} confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95{\%} CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95{\%} CI, 1.14-2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95{\%} CI, 1.06-1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95{\%} CI, 1.14-3.97) and soft distinct drusen (OR, 1.76; 95{\%} CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95{\%} CI, 1.10-2.04), soft indistinct drusen (OR, 1.84; 95{\%} CI, 1.09-3.10), and large drusen area (OR, 1.66; 95{\%} CI, 1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. Conclusions: This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.",
author = "Ronald Klein and Knudtson, {Michael D.} and Klein, {Barbara E K} and Wong, {Tien Y.} and Cotch, {Mary Frances} and Kiang Liu and Cheng, {Ching Y.} and Burke, {Gregory L.} and Saad, {Mohammed F.} and Jacobs, {David R.} and Sharrett, {A. Richey}",
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T1 - Inflammation, Complement Factor H, and Age-Related Macular Degeneration. The Multi-Ethnic Study of Atherosclerosis

AU - Klein, Ronald

AU - Knudtson, Michael D.

AU - Klein, Barbara E K

AU - Wong, Tien Y.

AU - Cotch, Mary Frances

AU - Liu, Kiang

AU - Cheng, Ching Y.

AU - Burke, Gregory L.

AU - Saad, Mohammed F.

AU - Jacobs, David R.

AU - Sharrett, A. Richey

PY - 2008/10

Y1 - 2008/10

N2 - Objective: To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Design: Population-based, cross-sectional study. Participants: We included 5887 persons aged 45 to 84 years with gradable AMD. Methods: Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Main Outcome Measure: Prevalence of AMD. Results: While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14-2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06-1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14-3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10-2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09-3.10), and large drusen area (OR, 1.66; 95% CI, 1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. Conclusions: This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

AB - Objective: To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Design: Population-based, cross-sectional study. Participants: We included 5887 persons aged 45 to 84 years with gradable AMD. Methods: Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Main Outcome Measure: Prevalence of AMD. Results: While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14-2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06-1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14-3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10-2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09-3.10), and large drusen area (OR, 1.66; 95% CI, 1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. Conclusions: This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

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