Genetic determinants of age-related macular degeneration in Middle Eastern populations: a systematic review

Age-related macular degeneration (AMD) is a leading cause of vision loss, with genetic factors playing a key role in disease susceptibility and progression. While extensive genetic research is being conducted, the genetic architecture of AMD in Middle Eastern populations remains understudied. This systematic review summarizes current evidence on genetic variants associated with AMD in Middle Eastern populations.

A comprehensive literature search was conducted in PubMed, Web of Science Core Collection, and Medline databases. Studies were included if they: (1) examined cohorts from Middle Eastern participants; (2) with clinically diagnosed AMD; (3) explored genetic variants or other genomic markers; (4) no restrictions on year of publication; and (5) were published in English.

The search yielded 449 articles (PubMed: 164, Web of Science: 99, Medline: 186). After removal of 221 duplicates, 228 unique articles were screened. Of these, 28 studies met the inclusion criteria, covering a total of 4,247 AMD cases and 3,447 controls from five countries: Turkey (n = 11), Iran (n = 11), Israel (n = 4), Jordan (n = 1), and Egypt (n = 1). Most analyses were targeted, with 25 studies targeting one to four genetic loci, two studies examining 12 variants, and one genome-wide association study. The most frequently studied genes were CFH, ARMS2, and HTRA1. The CFH Y402H variant (rs1061170) showed overall positive but heterogeneous associations with AMD risk across studied Middle Eastern populations, with reported odds ratios ranging from 0.36 to 17.34 and statistically significant p values ranging from <0.001 to 0.02 (total AMD cases and controls = 2,079). The ARMS2 A69 S variant (rs10490924) and HTRA1 promoter variant (rs11200638) demonstrated strong associations with neovascular AMD.

Few studies have examined genotype-phenotype correlations across this region, and many Middle Eastern countries lack published AMD genetic data. Consequently, the genetic landscape of AMD in the Middle East remains incompletely characterized. Available evidence suggests that variants in CFH, ARMS2, and HTRA1 are important AMD-associated loci in studied Middle Eastern populations, consistent with findings in other population groups.