Abstract
Background gp91phox, the catalytic core of NADPH oxidase (NOX) and biomarker of NOX activation, has been recently recognized as a parameter of systemic oxidative stress in several studies. Subclinical hypothyroidism (SH) is characteristic of elevated level of serum thyroid stimulating hormone (TSH) and is frequently accompanied with cholesterolemia. In this study, the levels of serum soluble gp91phox were measured to assess the oxidative stress in patients with SH. And the relationship among gp91phox, low-density lipoprotein-C (LDL-C), and TSH was also investigated. Methods A total of 51 subjects were enrolled and categorized into four groups: the healthy controls subjects (n = 13), controls with high level of LDL-C alone (n = 12), SH with normal level of LDL-C (n = 11), and SH with high level of LDL-C (n = 15). The related clinical and laboratory data were collected for statistical analysis. All the patients were newly diagnosed and did not take any medication. The information of lipid profile and thyroid function was extracted, and the concentrations of gp91phox were obtained with ELISA. Results The levels of serum soluble gp91phox evidently increased in the patients with SH with a high level of LDL-C (81.52 ± 37.00 ug/mL) as compared to the healthy controls (54.98 ± 1.83ug/mL, p < 0.001), controls with high level of LDL-C (61.21 ± 4.48 ug/mL, p=0.038) and SH with a normal level of LDL-C (62.82 ± 11.67ug/mL, p=0.027). Additionally, the levels of gp91phox showed a significant positive correlation with both the levels of LDL-C (r = 0.595, p < 0.001) and TSH (r = 0.346, p=0.013) by the Spearman correlation analyses. The correlation remained significant even when the effect of another factor was controlled (TSH: when the effect of LDL-C was controlled, r = 0.453, p=0.001; LDL-C: when the effect of TSH was controlled, r = 0.291, p=0.040). The main effect analysis showed an independent main effect of either LDL-C (p = 0.041) or TSH (p=0.022) on gp91phox without interaction (p=0.299). Conclusions Our work demonstrated that the levels of gp91phox, a novel biomarker for measuring the oxidative stress, were significantly elevated in the patients with SH. And LDL-C and TSH were both independent predictors of gp91phox. Abbreviations. BMI : Body mass index; TC : Total cholesterol; LDL-C : Low-density lipoprotein cholesterol; HDL-C : High-density lipoprotein cholesterol; TG : Triglyceride; FBG : Fasting blood glucose; FT3 : Free triiodothyronine; FT4 : Free thyroxine; TSH: Thyroid stimulating hormone; SBP : Systolic blood pressure; DBP : Diastolic blood pressure; SD : Standard deviation; LSD: Least significant difference.
Highlights
Subclinical hypothyroidism (SH) is referred to as the condition where the levels of serum thyroid stimulating hormone (TSH) are elevated and the concentrations of thyroid hormones are within the reference ranges
A Spearman correlation analysis revealed that the levels of TSH were positively correlated with those of low-density lipoprotein-C (LDL-C) (r 0.249, p 0.040) and total cholesterol (TC) (r 0.262, p 0.033) in the whole population of 51 subjects (Figure 1)
3.2. gp91phox Levels among the Four Groups. e levels of serum soluble gp91phox increased in the patients with SH with high level of LDL-C as compared to the healthy controls (81.52 ± 37.00ug/mL vs. 54.98 ± 1.83ug/mL, p < 0.001), controls with high level of LDL-C (81.52 ± 37.00ug/mL vs. 61.21 ± 4.48ug/mL, p 0.038), and SH with normal level of LDL-C (81.52 ± 37.00ug/mL vs. 62.82 ± 11.67ug/mL, p 0.027), indicating that the level of LDL-C or TSH might exert an effect on that of gp91phox
Summary
Subclinical hypothyroidism (SH) is referred to as the condition where the levels of serum thyroid stimulating hormone (TSH) are elevated and the concentrations of thyroid hormones are within the reference ranges. A growing number of studies have suggested that there is an increased risk of cardiovascular diseases in patients with SH [4, 5]. An imbalance in the equilibrium favoring the increased production of free radicals and diminished antioxidants, has been demonstrated to be elevated in SH [9]. The results are still scarce and somewhat controversial [10,11,12,13,14]. It has been correlated with a wide range of biological and pathological conditions [15], especially in the cardiovascular system [16]. Relevant reports are still missing on the concentrations of serum soluble gp91phox in SH
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