The association of glutathione S-transferase GSTT1 and GSTM1 gene polymorphism with pseudoexfoliative glaucoma in a Pakistani population

Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
Molecular vision (Impact Factor: 1.99). 10/2010; 16:2146-52.
Source: PubMed


The aim of the present study was to investigate the association of glutathione S-transferase GSTT1 and GSTM1 genotypes with pseudoexfoliative glaucoma (PEXG) in a group of Pakistani patients.
Multiplex polymerase chain reaction was used to study the GSTT1 and GSTM1 polymorphisms in 165 PEXG patients and 162 unaffected controls.
In the current study we describe a significant gender-specific association of GSTT1 and GSTM1 null genotypes with PEXG. The three null genotype combinations (i.e., T1M0, T0M1, and T0M0) were found at significantly higher frequencies in the PEXG patients as compared to the controls (χ(2)=21.82, p<0.001). This association was specifically related to the female patients (χ(2)=35.63, p<0.001); no such association was seen in the male patients (χ(2)=2.28, p>0.05).
The results suggest that there is a significant involvement of the GSTT1 and GSTM1 polymorphisms in female Pakistani patients having PEXG, which suggests a possible gender-specific impairment of detoxification in this group.

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    • "DNA was isolated, using a phenol-chloroform protocol (Khan et al., 2010). Isolated DNA was electrophoresed on 1% agarose gels and stained with ethidium bromide. "
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    ABSTRACT: Deletions in GSTM1 and GSTT1 genes are considered to be a risk factor for cancer development but the exact location of these deletions in the genome was unknown. Three main objectives of the current study were to: (a) identify the boundaries of these deletions in the human genome, (b) screen homozygous (-/-) and heterozygous (+/-) deleted, as well as homozygous present (+/+) individuals using PCR assays, (c) detect associations of pharyngeal (PC) and laryngeal cancer (LC) with the respective genotypes. In total, 102 PC and 92 LC patients were screened and compared with 150 controls. PCR mapping and sequencing revealed a 6 kbp deletion for GSTM1 and a 9 kbp deletion for the GSTT1 gene. The mean age of PC cases was 48.1 (±16.7) years; for LC cases it was 48.5 (±17.4) years and for controls 46 (±17.7) years. The OR (odds ratio) for the GSTM1 null genotype in PC and LC cases was 10.2 and 1.0 (95% CI 5.04-20.7 and 1.1-1.7) respectively. Similarly, for GSTT1 the OR was 4.02 with a 95% CI of 2.3-7.1 in PC cases. For LC cases the OR was 0.8 with 95% CI of 0.4-1.7. A non-significant number of LC and PC patients had heterozygous deletions of GSTM1 compared to controls (OD 0.5, 95% CI 0.2- 1.6 and OR 0.5, 95% CI 0.2- 1.5 respectively). The GSTT1 gene also showed a non-significant association in PC (OD 0.9, 95% CI 0.4-1.9), as well as in LC patients (OD 0.7, 95% CI 0.3-1.7). The homozygous genotype was significantly associated with PC and LC, whereas the heterozygous was not so. The GSTM1 (-/-) and GSTT1 (-/-) genotypes are a risk factor for LC and PC, whereas the (+/-) genotypes are not.
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    • "Polymorphisms of GST have been detected in POAG [52], cataract [53], and exudative age-related macular degeneration [54]. However, in patients with PXG of Turkish [55], Swedish [56], and Arab [57] populations, no significant association was noted. Recently, it was shown that the M0 and T0 phenotype of GST is strongly associated with PXG in female Pakistani patients [56]. "
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    • "In previous studies we have identified significant associations with polymorphisms in the glutathione S-transferase (GSTT1 and GSTM1) [21] and tumor necrosis factor alpha (TNF-α) [12] with PEXG. Among these higher OR was observed for TNF-α (8.37) as compared to LOXL1 (6.98), GSTT1 (4.26), and GSTM1 (3.81), the combined effect of all these genes probably have a significant contribution in causing PEXG in the Pakistani cohort. "
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