ArticleEJIFCC2026
Population-Specific Reference Intervals for Whole-Blood GSH/GSSG Ratio in Healthy Emirati Adults According to CLSI and ISO 15189 Guidelines.
Article in EJIFCC, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The glutathione redox system, expressed as the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), is a key indicator of cellular oxidative status. Manufacturer-provided reference intervals are typically derived from non-local populations and may not be applicable across different ethnic and geographic groups. Objective: To characterize the distribution of whole-blood GSH/GSSG ratio in healthy Emirati adults using ultra-high-performance liquid chromatography (UHPLC) and to establish population-specific reference intervals in accordance with CLSI C28-A3 and ISO 15189 guidelines. Methods: In this cross-sectional study, whole-blood samples from 120 apparently healthy Emirati adults were analyzed using a commercial UHPLC assay. The GSH/GSSG ratio was calculated for each participant. Due to non-normal distribution, reference intervals were derived using a nonparametric approach. Both the conventional 95% reference interval (2.5th-97.5th percentiles) and the central 90% interval (5th-95th percentiles) were calculated. Bootstrap resampling (20,000 iterations) was used to estimate 95% confidence intervals for the central 90% limits. Results: The GSH/GSSG ratio demonstrated a right-skewed distribution with a median (IQR) of 4.76 (3.58-6.77). Most participants (89.2%) had values below the manufacturer-reported reference interval (10-15), with only 5.0% within this range. The nonparametric 95% reference interval was 1.66-28.40. The central 90% interval was 2.53-17.20, with bootstrap 95% confidence intervals of 2.21-2.97 (lower) and 14.92-19.73 (upper). Conclusion: Manufacturer-provided reference intervals do not reflect the distribution observed in healthy Emirati adults. Population-specific reference intervals are therefore necessary. Reporting both 95% and 90% intervals, supported by bootstrap estimates, enhances clinical interpretation for both diagnostic and screening applications.
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