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Polymorphic Glutathione S-Transferases as Genetic Risk Factors for Senile Cortical Cataract in Estonians

¹ From the Department of Human Biology and Genetics, Institute of General and Molecular Pathology, and ² Department of Ophthalmology, University of Tartu; and ³ Department of Ophthalmology, Tartu Outpatient Hospital, Tartu, Estonia.

PURPOSE. To investigate the possible association between glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 polymorphism and the occurrence of age-related cataracts in Estonian patients.

METHODS. Patients with cortical (155), nuclear (77), posterior subcapsular (120), mixed type (151) of senile cataract and control individuals (202) were phenotyped for GSTM1 and GSTT1 by enzyme-linked immunosorbent assay and genotyped for GSTM3 and GSTP1 by polymerase chain reaction.

RESULTS. The frequency of the GSTM1-positive phenotype was significantly higher in the cortical cataract group (60.6%) than in the controls (45.0%) with odds ratio of 1.88 (95% CI, 1.23–2.94; P = 0.004). The cortical cataract risk associated with the GSTM1-positive phenotype was increased in carriers of the combined GSTM1-positive/GSTT1-positive phenotype (OR = 1.99; 95% CI, 1.30–3.11; P = 0.002) and the GSTM1-positive/GSTM3 AA genotype (OR = 2.28; 95% CI, 1.51–3.73; P < 0.001). The highest risk of cortical cataract was observed in patients having all three susceptible genotypes (OR = 2.56; 95% CI, 1.59–4.11; P < 0.001). Also, a significant interaction between the presence of the GSTP1* A allele and cortical cataract was found with prevalence of the GSTP1* A allele among the cortical cataract cases compared with the controls. Ninety-five percent of subjects with cortical cataract had the GSTP1 (AA, AB, or AC) genotype, whereas in controls 87% of persons had a genotype with GSTP1*A allele (OR = 3.1; 95% CI, 1.31–7.35; P = 0.007). In contrast to the GSTP1*A allele, the presence of the GSTP1*B allele in one or two copies leads to decreased cortical cataract risk (OR = 0.09 for GSTP1 BB genotype).

CONCLUSIONS. The GSTM1-positive phenotype as well as the presence of the GSTP1*A allele may be a genetic risk factor for development of cortical cataract.

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