Estrogen receptor alpha gene polymorphisms associated with incident aging macula disorder

Area of Science:

• Ophthalmology
• Genetics
• Endocrinology

Background:

• Aging-macula disorder (AMD) is a leading cause of irreversible vision loss.
• Early menopause has been suggested to increase AMD risk, while estrogen exposure may reduce it.
• The role of estrogen receptor alpha (ESR1) gene variations in AMD development requires further investigation.

Purpose of the Study:

• To examine the association between ESR1 PvuII-XbaI haplotypes and the incidence of AMD.
• To determine if specific genetic variations in ESR1 influence AMD risk.

Main Methods:

• Prospective population-based cohort study (Rotterdam Study) with 4571 participants aged 55+.
• Analysis of ESR1 PvuII-XbaI haplotypes and incident early or late AMD over a mean follow-up of 7.7 years.
• Cox proportional hazards regression used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for confounders.

Main Results:

• ESR1 PvuII-XbaI haplotype 1 was identified as a significant risk factor for late AMD.
• Individuals with two copies of haplotype 1 exhibited a 3.20-fold increased risk of late AMD (adjusted for age and sex).
• The risk was more pronounced for wet AMD (HR 4.29), even after adjusting for multiple confounders including smoking and complement factor H genotype.

Conclusions:

• Carriers of ESR1 PvuII-XbaI haplotype 1 have a heightened risk of developing late AMD.
• The association is particularly strong for the wet subtype of late AMD.
• Genetic variations in ESR1 may play a role in AMD pathogenesis, especially concerning estrogen signaling pathways.