Abstract
Purpose :
Cataracts are a clinically heterogeneous disorder affecting up to 12% of the population aged 40 years and older. Multiple environmental and genetic factors influence disease susceptibility. Glutathione S-transferase (GST) genes deletion might be involved in cataractogenesis, through impaired conjugation of reduced glutathione. Excessive ROS could promote earlier lens opacification. To date, no systematic studies have assessed the effect of GST polymorphisms and age of onset of cataracts. Here, we aim to evaluate the association between GST polymorphisms, found through a systematic review, on cataracts age of presentation by meta-analysis.
Methods :
We conducted a systematic search in MEDLINE, HuGENET, and LILACS databases. We included observational studies that determined genotype based on validated genotyping instruments and with a stringent quality check (e.g., genotyping call rate ≥ 95%, HWE in controls). We abstracted counts of null alleles of GSTM1 and GSTT1 in cases and controls. We performed a meta-analysis of these measurements using random and fixed effects models, subgrouping by age of diagnosis.
Results :
So far, we have evaluated two GST genes with null alleles, GSTM1 and GSTT1. Pooling both in a fixed-effects model, GST genes are significantly associated with increased odds of cataract (Overall: 1.05 1.16 1.28 p<0.01; GSTM1: 1.04 1.17 1.32 p <0.01, and GSTT1: 0.91 1.12 1.36 marginally significant). Asians have greater odds for cataracts among those null carriers compared to positive alleles (OR: 1.21 1.76 2.55). GSTM1 positive allele is significantly more prevalent and thus is protective of cataract in cases between 50 to 60 years old. GSTT1 null allele, on the other hand, increases the odds of cataract by a factor of 1.76 at 50 years of age (OR: 1.21 1.76 2.55).
Conclusions :
We have preliminary evidence with moderate heterogeneity that GST genes are significantly linked to cataract and age of onset. GSTM1 and GSTT1 null allele compared to positive carriers have significantly more odds for early or late age of cataract onset, respectively. Further replication and clinical applicability of these results merit study.
This is a 2020 ARVO Annual Meeting abstract.