Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population.

This study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.3) were analyzed for SNP-based and haplotype association using SHEsis online software. Single-SNP-based association analysis showed three SNPs have a statistically significant association with beta-thalassemia. When Bonferroni correction was applied, four SNPs were found statistically significant with beta-thalassemia; IVS2-74T>G (padj = 0.047), IVS2-16G>C (padj = 0.017), IVS2-666C>T (padj = 0.017) and 3'UTR + 314G>A (padj = 0.002). However, 3'UTR + 233G>C did not yield a significant association with padj value = 0.076. Further investigation using combined five SNPs for haplotype association analysis revealed three susceptible haplotypes with significant p values of which, haplotypes 1-2-2-1-1 (p = 6.49 × 10-7, OR = 10.371 [3.345-32.148]), 1-2-1-1-1 (p = 0.009, OR = 1.423 [1.095-1.850] and 1-1-1-1-1 (p = 1.39 × 10-4, OR = 10.221 [2.345-44.555]). Three haplotypes showed protective effect with significant p value of which, 2-2-1-1-1 (p = 0.006, OR = 0.668 [0.500-0.893]), 1-1-2-2-1 (p = 0.013, OR = 0.357 [0.153-0.830]) and 1-1-2-1-1 (p = 0.033, OR = 0.745 [0.567-0.977]). This study has identified the potential use of intragenic polymorphic markers in the HBB gene, which were significantly associated with beta-thalassemia. Combining these five SNPs defined a new haplotype model for beta-thalassemia and further evaluation for predicting severity in beta-thalassemia.

The Effects of Fixed Combination of Bimatoprost-Timolol and Travoprost-Timolol on Intraocular Pressure in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension, Previously on Nonfixed Combination of Latanoprost and Timolol.

PURPOSE: To compare the effects of fixed combination of bimatoprost-timolol and travoprost-timolol on intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. DESIGN: This was a prospective, randomized, observer-masked, crossover parallel comparison trial. METHODS: Forty-one patients with primary open-angle glaucoma or ocular hypertension on nonfixed combination of latanoprost and timolol with IOP of 21 mm Hg or less were randomized to either bimatoprost-timolol or travoprost-timolol fixed combinations for 8-week treatment period. Intraocular pressure was measured at 8 AM, 12 PM, 4 PM, and 8 PM at the baseline and at the end point. Conjunctiva hyperemia and superficial punctate keratopathy after treatment with each fixed combination therapy were assessed and compared with the baseline. Patients were then switched to the opposite drug without a medication-free period for another 8-week, and diurnal IOP measurement was repeated. RESULTS: Bimatoprost-timolol fixed combination reduced the baseline mean diurnal IOP statistically significantly from 17.3 mm Hg [95% confidence interval (CI), 16.8-17.7 mm Hg] to 16.4 mm Hg (95% CI, 15.9-17.0 mm Hg) (P = 0.036). Travoprost-timolol fixed combination lowered the mean diurnal IOP to 17.1 mm Hg (95% CI, 16.5-17.7 mm Hg), but it was not significant. Direct comparison between the 2 fixed combinations showed no significant difference. Both fixed combinations had no significant effect on conjunctiva hyperemia. Interestingly, patients on travoprost-timolol fixed combination had significantly less superficial punctuate keratopathy (P = 0.012). CONCLUSIONS: Both fixed combination of bimatoprost-timolol and travoprost-timolol had no significantly different ocular hypotensive effect. However, bimatoprost-timolol fixed combination produced additional IOP lowering in patients previously treated with nonfixed combination of latanoprost and timolol.