Approximately 80% of all cataracts are age-related and idiopathic. Depending on the location of the opacity within the lens, ARC is termed cortical, nuclear, or subcapsular. There are also forms of mixed cataract that feature more than one morphological sign. In general, maintenance of an intact, transparent lens requires balanced homeostasis of metabolic components.
8 ARC is considered a multifactorial disease in which environmental components and genetic predisposition contribute to the development of the pathologic condition. Interactions between these factors are likely, and knowledge of the cause of ARC may provide crucial information for the prevention of and potential therapy for the disease. Among environmental risk factors are smoking, exposure to UV-B radiation, and alcohol.
9 In addition, physiological conditions such as age, sex, diabetes, high body mass index, persistent intraocular inflammation, prolonged corticosteroid administration, and oxidative damage seem to promote the development of ARC.
9 In light of this complexity, knowledge of genetic risk factors is still scarce. Variants of the detoxifying enzymes arylamine
N-acetyltransferase-2 and glutathione-
S-transferase (GST) were found to be associated with ARC.
10–12 Furthermore, two sequence variants in the vicinity of the 3′ end of the gene for Eph-receptor tyrosine kinase type A2 (
EPHA2) were shown to associate with both childhood and age-related forms of cataract.
13 Recently, a mutation in the gene encoding αA-crystallin was reported to be associated with ARC because of the loss of chaperone-like activity.
14 SNP-based allele frequencies and, consequently, association with a disease phenotype vary often among different ethnic groups, exemplified by a sequence variant in the gene encoding galactokinase, an enzyme involved in galactose metabolism
15,16 and GST.
10,11,17 Similarly, heat-shock transcription factor 4 may be involved in ARC in an Asian population.
18