Sushma Ravindra Umrao, Sampathkumar Elangovan, Muhammad Raza Qureshi, Muhammad Masoud Alam, Farhan Ashraf, Shafaath Husain Syed Mohammed, Mohamed Sayed Tharammal, Faiz Ul Amin, Mohammed Munir Khan
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.
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.