Clinical characteristics and analysis of HFE gene variants (C282Y and H63D) in Jordanian Arab patients with age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a complex genetic disorder with multiple etiologies. Multiple genes as well as environmental effects are thought to play a role in causing AMD. Recent evidence pointed that elevated iron overload, resulting from hereditary defects of iron homeostasis, is associated with retinal degeneration and consequently plays a role in the pathogenesis of AMD. Hemochromatosis is a genetic disorder in which excess iron is absorbed from the diet and deposited in different tissues, primarily caused by mutations in HFE gene. Two major mutations in HFE are responsible for most hemochromatosis cases, namely, C282Y and H63D. In this work we gathered information relating to 37 AMD patients from Jordan, and investigated the potential association between hemochromatosis, or more specifically, carrier state for a mutation in HFE gene (which may moderately increase dietary iron absorption) and AMD, given the effect of elevated iron levels on AMD occurrence. Questionnaires and blood samples were collected from patients visiting the eye care clinic in the King Abdullah hospital in Jordan. DNA was extracted from patient samples and mutations in HFE were genotyped (using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and DNA sequencing) and compared to 106 control samples. We could not detect C282Y (rs1800562) variant in our patient population or in the controls. For carrier status with H63D (rs1799945) we had 30.3% compared to a frequency of 22.7% in the controls (p= 0.37). H63D allele frequency was 15.2% in our patients compared to 11.8% in the controls (p=0.30). H63D variant seems to be more frequent in AMD patients though not reaching a significance of p= 0.05. To date, this is the first attempt to link HFE (particularly, H63D) mutation to AMD.

Keywords: AMD; HFE; C282Y; H63D; Association; Polymorphism

The Egyptian Journal of Medical Human Genetics (2013) 14, 177–181