Family History, Cardiovascular Disease Linked to Risk of Age-Related Macular Degeneration

New research has identified several genetic and environmental risk factors for age-related macular degeneration (AMD), including family history and cardiovascular disease.

A team, led by Priscila H. H. Rim, Department of Ophthalmology, School of Medical Sciences, University of Campinas (UNICAMP), identified the association between AMD and genetic and environmental risk factors in a cohort of patients from Brazil.

Risk Factors

Some major risk factors for AMD include genetics, demography, nutrition, lifestyle, other environmental factors, and ocular factors. However, age is the strongest risk factor for AMD.

A lot of past research has also focused on family history as a major risk factor.

In the cross-sectional study, the investigators collected data from 236 patients at least 50 years of age, 141 of which were diagnosed with AMD and the remaining 95 participants as part of the control group. Of the patients with AMD, 70% (n = 99) had advanced AMD in at least 1 eye (57% neovascular AMD and 13% geographic atrophy), and 30% (n = 42) had not-advanced AMD. 

The mean age of all participants was 73.6±7.9 years, but the mean age of the AMD group was 74.4±8.1 years, compared to 72.24±7.4 years for the control group (OR, 1.51; 95% CI, 0.88–2.58).

The investigators obtained data on the patients using a questionnaire, which included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits.

They also conducted genetic evaluations including direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants.

The investigators also performed a risk assessment of environmental risk factors and genetic variants linked to AMD and used multiple linear regression analysis to determine correlations between AMD and the data.

Family History and Cardiovascular Disease

The investigators found family history of AMD (OR, 6.58; 95% CI, 1.94–22.31), presence of cardiovascular disease (OR, 2.39; 95% CI, 1.08–5.28), low physical activity level (OR, 1.39; 95% CI, 0.82–2.37), and high serum cholesterol (OR, 1.49; 95% CI, 0.84–2.65) were linked to an increased risk of disease.

They also observed a significant association between cardiovascular disease and the incidence of advanced AMD (OR, 2.29; 95% CI, 0.81–6.44).

They also found an odds ratio of 2.21 (95% CI, 1.47-3.35) for the risk allele of the LOC387715 gene, while the OR for the CFH gene was 2.27 (95% CI, 1.52-3.37) and the OR for the HTRA1 gene was 2.76 (95% CI, 1.89-4.03).

Using a stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and cardiovascular disease were all linked to an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype.

“The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population,” the authors wrote.

The study, “Correlation between genetic and environmental risk factors for age-related macular degeneration in Brazilian patients,” was published online in PLOS One.