by Karpova N.S. | The Institute of General Pathology and Pathophysiology, Moscow, Russia
Motivation and Aim:
Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of
visual impairment in developed countries. Risk factors include environmental components
and genetic determinants. 50% or more of the risk of developing AMD is due to mutations in
the region of 2 genes, CFH and ARMS2/HTRA1. However, the exact mechanisms of
pathology development, in particular the role of mutations in the ARMS2 gene region,
remain not fully understood, as well as the functions of the protein. A number of
polymorphisms related to ARMS2 associated with the risk of developing AMD were
identified in several GWASs at once . In this regard, we decided to determine the putative
AMD risk haplotype, its prevalence, and compare it with the prevalence of early and late
stages of AMD.
Results:
An analysis of the GWAS-catalog and literature made it possible to reduce the number of
studied polymorphisms to 5 (rs3750846, rs10490924, rs3750847, rs3750848, rs61871744),
since only they are associated with AMD and are located in the region of the gene itself.
When assessing the prevalence of possible haplotypes, a possible AMD risk haplotype was
determined, for which the prevalence was 0,1899 or 18,99% (taking into account the AMD
risk alleles, rs10490924-T and rs3750847-T). his risk haplotype will occur in the
homozygous state with a frequency of 3,6% (which is close to the prevalence of early AMD
3,5% aged 55–59 years) and in the heterozygous state with a frequency of 30,5% (which is 2
times higher than the prevalence of late AMD at the age of ≥85 years).