MyVisionTest News Archive
Nov 13, 2008
Systemic inflammatory disease not strongly associated with AMD
A large prospective multi-ethnic study failed to find a strong association between systemic inflammatory disease, use of antiinflammatory agents, biomarkers of inflammatory disease, and related processes with age-related macular degeneration (AMD).
Inflammation has been hypothesized to have a role in the pathogenesis of AMD. Inflammatory cells are thought to cause microvascular injury by direct release of long-acting oxidants, toxic oxygen compounds, and proteolytic enzymes that damage Bruch’s membrane. However, data from clinical and epidemiologic studies regarding the relation of systemic inflammation and AMD have been inconsistent.
Recent genetic studies have also shown that a Y402H polymorphism in the complement factor H (CFH) gene on chromosome 1q is strongly associated with AMD, suggesting a role of innate immunity and inflammation in its pathogenesis. Although a considerable body of information has been developed regarding the CFH gene and inflammatory factors in whites, less is known regarding the distribution of these genes and their relation to AMD in other racial/ethnic groups in the general population.
This study included 5887 persons with AMD from the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a prospective cohort study of men and women aged 45–85 years without a history of clinical cardiovascular disease (CVD) living in 6 United States communities. The study objectives of the MESA are to identify risk factors for subclinical CVD, progression of subclinical CVD, and transition from subclinical to clinical CVD. 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.
While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. 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.
In attempting to explain their findings, the investigators speculate that it is possible that inflammation may play a larger role in the pathogenesis of progression to late AMD rather than initiating the earlier stages of the disease. It is also possible that inflammation occurring earlier in life initiates processes involved in the pathogenesis of early AMD and this relationship is not detected in the cross-sectional examination of persons studied later in life.
The researchers have previously reported that racial/ethnic differences in the frequency of early AMD exist in the MESA cohort, with decreasing overall frequencies found in whites (5.4%), Chinese (4.6%), Hispanics (4.2%), and blacks (2.4%). The reasons for these racial/ethnic differences, especially between whites and blacks, were not explained by known risk factors such as cigarette smoking, history of alcohol drinking, BMI, hypertension, diabetes status, and markers of subclinical CVD.
The current research study showed that a history of inflammatory diseases or use of antiinflammatory agents, or biomarkers of inflammation and related processes also did not explain racial/ethnic differences in prevalence of early AMD among the different racial/ethnic groups.
Whites, blacks, and Hispanics who were all homozygous for the CFH Y402H CC variant genotype had the highest frequencies of early AMD compared with those with the CFH Y402H TT wild genotype. But this finding does not explain the difference in AMD prevalence between whites and blacks.
Read more...
Ophthalmology 2008;115:1742–1749
Tags: complement, genetics, racial differences, AMD
A large prospective multi-ethnic study failed to find a strong association between systemic inflammatory disease, use of antiinflammatory agents, biomarkers of inflammatory disease, and related processes with age-related macular degeneration (AMD).Inflammation has been hypothesized to have a role in the pathogenesis of AMD. Inflammatory cells are thought to cause microvascular injury by direct release of long-acting oxidants, toxic oxygen compounds, and proteolytic enzymes that damage Bruch’s membrane. However, data from clinical and epidemiologic studies regarding the relation of systemic inflammation and AMD have been inconsistent.
This study included 5887 persons with AMD from the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a prospective cohort study of men and women aged 45–85 years without a history of clinical cardiovascular disease (CVD) living in 6 United States communities. The study objectives of the MESA are to identify risk factors for subclinical CVD, progression of subclinical CVD, and transition from subclinical to clinical CVD. 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.
While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. 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.
In attempting to explain their findings, the investigators speculate that it is possible that inflammation may play a larger role in the pathogenesis of progression to late AMD rather than initiating the earlier stages of the disease. It is also possible that inflammation occurring earlier in life initiates processes involved in the pathogenesis of early AMD and this relationship is not detected in the cross-sectional examination of persons studied later in life.
The researchers have previously reported that racial/ethnic differences in the frequency of early AMD exist in the MESA cohort, with decreasing overall frequencies found in whites (5.4%), Chinese (4.6%), Hispanics (4.2%), and blacks (2.4%). The reasons for these racial/ethnic differences, especially between whites and blacks, were not explained by known risk factors such as cigarette smoking, history of alcohol drinking, BMI, hypertension, diabetes status, and markers of subclinical CVD.
The current research study showed that a history of inflammatory diseases or use of antiinflammatory agents, or biomarkers of inflammation and related processes also did not explain racial/ethnic differences in prevalence of early AMD among the different racial/ethnic groups.
Whites, blacks, and Hispanics who were all homozygous for the CFH Y402H CC variant genotype had the highest frequencies of early AMD compared with those with the CFH Y402H TT wild genotype. But this finding does not explain the difference in AMD prevalence between whites and blacks.
Read more...
Ophthalmology 2008;115:1742–1749
