Abstract
Purpose::
Significant interactions between the Y402H polymorphism in the complement factor H (CFH) gene and modifiable risk factors such as smoking status and body mass index (BMI) have been reported for advanced age-related macular degeneration (AMD). These interactions have not been tested for early AMD. This study examines genetic and environmental risk due to CFH, smoking status, BMI, and high blood pressure in early bilateral AMD.
Methods::
Prevalent early AMD cases (n=101) and control subjects (n=595) were ascertained from the Los Angeles Latino Eye Study (LALES). Early AMD cases were identified by the presence of intermediate to large soft drusen in both eyes by masked grading of fundus photographs. Subjects were categorized as smokers if former or current smoking was reported during the study visit. BMI and high blood pressured were calculated from recorded height, weight, systolic (SBP) and diastolic (DBP) blood pressure measurements. A BMI of <25kg/m2 was classified as normal, 25 to <30 overweight, 30 to <40 obese, and ≥40 morbidly obese. High blood pressure was defined as having a SBP ≥140mmHg or DBP ≥90mmHg. The proportion of H alleles was compared among cases and controls. Homogeneity tests were used to determine if this relationship varied by environmental factors.
Results::
CFH (HH/HY vs. YY, OR=1.71(1.11-2.63)) was associated with early AMD after controlling for age and gender. High blood pressure (OR=1.73(1.08-2.78)) and age (60-69 years vs. 40-49 years, OR=1.90(1.04-3.49); ≥70 years vs. 40-49 years, OR=1.87(1.00-3.48)) significantly increased risk for early AMD. High blood pressure did not significantly alter the relationship between CFH and early AMD (high blood pressure, 45.7% AMD vs. 31.5% controls, p=0.12; regular blood pressure, 43.9% AMD vs. 32.3% controls, p=0.06; test of homogeneity p=0.82). There was no significant increase in risk for early AMD by BMI or smoking status. No differences were found in the prevalence of early AMD by the presence of the H allele and smoking status.
Conclusions::
The CFH H-allele and high blood pressure do not interact to increase risk for early bilateral AMD in a population-based sample of Latinos.
Keywords: age-related macular degeneration • gene modifiers • candidate gene analysis