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Published on: July 14, 2016
Inflammation, complement factor h, and age-related macular degeneration: the Multi-ethnic Study of Atherosclerosis
Ronald Klein1, Michael D Knudtson, Barbara E K Klein
1Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726-2397, USA. kleinr@epi.ophth.wisc.edu
Insights
This study found the CFH Y402H gene variant is associated with age-related macular degeneration (AMD) in nonwhite populations. However, inflammatory factors did not link to AMD, and ethnic differences in prevalence remain unexplained.
Area of Science:
- Ophthalmology
- Genetics
- Immunology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- The role of systemic inflammation and genetic factors, particularly the complement factor H (CFH) Y402H variant, in AMD prevalence across diverse ethnic groups requires further investigation.
Purpose of the Study:
- To investigate the association between systemic inflammatory disease, CFH Y402H genotype status, and AMD prevalence in a multiethnic cohort.
- To explore potential ethnic variations in AMD prevalence and its contributing factors.
Main Methods:
- A population-based, cross-sectional study involving 5887 participants aged 45-84 years with gradable AMD.
- AMD was assessed using digital fundus photography.
- Biomarkers of inflammation, history of inflammatory diseases, and anti-inflammatory agent use were collected.
Main Results:
- No significant associations were found between systemic inflammatory factors and overall AMD severity after controlling for covariates.
- Elevated high-sensitivity C-reactive protein and interleukin-6 levels were linked to geographic atrophy.
- The CFH Y402H CC variant genotype was associated with higher early AMD frequency in whites, blacks, and Hispanics.
- CFH genotype frequency partially explained prevalence differences between Chinese and Hispanics compared to whites, but not between whites and blacks.
Conclusions:
- The Y402H CFH gene variant is confirmed to be associated with AMD in nonwhite populations.
- The study did not elucidate the lack of association between inflammatory factors and AMD or the reasons behind observed ethnic differences in AMD prevalence.
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.
