Molecular Genetic Studies of Glaucomas in South India

Abstract

Abstract: : Purpose: Primary angle closure (PACG) and open angle (POAG) glaucomas are equally distributed in the south Indian patients. Molecular genetic basis of the disease in this population is less understood and hence this study. Methods: Samples were drawn from a hospital and population-based screening program. After complete ophthalmic examination DNA from 60 patients [36:POAG, 4: Juvenile open angle glaucoma (JAOG) and 20: Ocular hypertension (OHT)] were screened for TIGR/MYOC and optineurin gene mutations. Ninety-five patients (65: POAG, 7: JOAG and 23: OHT) were screened for the association of polymorphism in glutathione S transferase gene for glaucoma susceptibility. Fifteen PACG families with 2 or more affected members were included for whole genome search (WGS). Results: Six nucleotide variations in the MYOC gene were observed. Two variations in promoter region: C to T at -15 bp and ^∐ A between -18 and -17 bp upstream to the transcription start site in fourteen and six patients respectively. Twenty-two patients with (G to A; N76K) and two patients with (G to T; Q48H) in exon 1; 16 patients with IVS2 795+35 A to G and 5 patients with + 276 del A in 3' UTR were observed. The novel nucleotide variation was not seen in thirty-five unrelated healthy controls but the other variations were polymorphisms. The frequency of the GSTM1 positive individuals among the glaucoma (87%) was significantly higher than in controls (56%) with an odds ratio of 5.29 (95% CI 1.85-15.83; p =0.00024). Partial genome search for PACG has not resulted in any linkage. Conclusions: TIGR/MYOC gene is responsible for mutations in 2.5% of south Indian OAG patients. We suggest that GSTM1 polymorphism could be associated with the development of OAG. In the WGS, the clinical criteria for PACG patients are revised for homogeneity.

Keywords: genetics • mutations • linkage analysis