Ke Chen,1 Xuesong Fan,1,2 Junyi Wu,1 Siyu Chen,1 Jiashu Yang,1 Linlin Shen,1 Zihan Liu,1 Hui Yuan1 

1Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence: Hui Yuan, Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, People’s Republic of China, Email 18911662931@189.cn

Purpose: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine mostly linked to pathological conditions including inflammation, myocardial ischemia, and cancer. We aimed to establish reference intervals (RIs) for GDF-15 in a large, multicenter cohort of apparently healthy Chinese individuals.
Patients and Methods: Adopting unified and stringent criteria, 8,488 eligible subjects from six representative cities in China were enrolled. Serum GDF-15 concentrations were measured with the Maccura Biotechnology i3000 automatic chemiluminescence analyzer and its corresponding reagents. Outliers were identified using the Tukey’s test. To determine the need for partitioning by age and sex, we conducted a two-level nested analysis of variance (ANOVA), considering an standard deviation ratio (SDR) > 0.3 as indicative of notable subgroup differences. The 2.5th and 97.5th percentiles of the RIs were established using non-parametric statistical methods, with 90% confidence interval.
Results: A total of 7,764 participants were included in the data analysis, with 724 outliers excluded. GDF-15 levels displayed a skewed distribution as confirmed by the Kolmogorov–Smirnov test. GDF-15 levels increased with age (All P < 0.001) and were higher in males than in females (all P <  0.001, except 18– 29 years, P =  0.373). The SDR from the two-level nested ANOVA for different age intervals and sex were 0.83 and < 0.01. Age- and sex-specific RIs for serum GDF-15 were established based on the study cohort.
Conclusion: Our study indicates that GDF-15 levels in the Chinese population are comparable to those observed in European populations, with the exception of sex-based differences.

Keywords: growth differentiation factor 15, non-parametric method, reference intervals