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ORIGINAL ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 6  |  Page : 26-31  

Serum paroxonase 1 level may be an indicator and predictor of the severity of androgenetic alopecia


1 Department of Dermatology, Andrology and STDs, Mansoura University, Mansoura, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission05-Aug-2020
Date of Decision05-Nov-2021
Date of Acceptance13-Oct-2021
Date of Web Publication22-Nov-2021

Correspondence Address:
Marwa Zohdy
Mansoura University, Mansoura 35516
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijt.ijt_128_20

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   Abstract 


Background: Androgenetic alopecia (AGA) is a common stressful form of hair loss caused by androgen excess, genetic factors, and exposure to oxidative stress (OS) with the formation of reactive oxygen species (ROS). Paraoxonase 1 (PON1) is an enzyme synthesized in the liver bound to high-density lipoproteins to prevent lipid peroxidation. Aim: The aim of our work is to estimate serum PON1 level in patients with AGA and correlate its levels with disease severity which may help in determining if there is a role of ROS in pathogenesis of AGA. Subjects and Methods: This study was carried out as a case and control on 40 patients with AGA (diagnosed by typical clinical and dermoscopic finding) versus 40 control subjects. Blood samples were taken from all subjects to assess serum PON1enzyme using enzyme-linked immunosorbent assay kits. Results: There was a significant decrease in serum PON1 concentration level in AGA patients in comparison to controls, in addition, there was a significant decrease correlated with AGA severity (P < 0,001). The study proved that PON1 is considered highly sensitive and specific for AGA cases and a good predictive factor of AGA in healthy subjects. Conclusion: This is the first study done to reveal that the level of PON1 significantly decreased in AGA patients, which may give additional proof that OS has role in the pathogenesis of AGA and hence may help in the management of AGA by adding antioxidants in treatment.

Keywords: Androgenetic alopecia, antioxidants, oxidative stress, paraoxonase 1, reactive oxygen species


How to cite this article:
Tantawy M, Khabir AA, Mahsoub N, Zohdy M. Serum paroxonase 1 level may be an indicator and predictor of the severity of androgenetic alopecia. Int J Trichol 2021;13:26-31

How to cite this URL:
Tantawy M, Khabir AA, Mahsoub N, Zohdy M. Serum paroxonase 1 level may be an indicator and predictor of the severity of androgenetic alopecia. Int J Trichol [serial online] 2021 [cited 2021 Dec 6];13:26-31. Available from: https://www.ijtrichology.com/text.asp?2021/13/6/26/330776




   Introduction Top


Androgenetic alopecia (AGA) is a common form of hair loss occurring in 80% of men and 50% of women.[1] It is experienced as a moderately stressful condition that diminishes body image satisfaction.[2] It is characterized by a progressive reduction in the diameter, length, and pigmentation of hair due to androgen excess, genetic factors, and exposure to oxidative stress (OS) with the formation of reactive oxygen species (ROS).[3] It is thought that lipid peroxidation, glutathione derivatives, and nitric oxide are indicators of cellular destruction by ROS.[4]

Inflammation is suggested to be a feature in AGA, evidenced by the presence of activated T-cells infiltrating the lower portions of follicular infundibula, with concentric layers of perifollicular collagen deposition, in 40% of cases of AGA versus 10% of normal controls.[5] A considerable difference in the inflammatory infiltrate has been observed between balding and nonbalding scalp.[6]

Paraoxonase 1 (PON1) is a member of a family of proteins that also includes PON2 and PON3.[7] It is an enzyme synthesized in the liver and has lactonase and esterase activities toward lipid peroxides and circulates in plasma bound to high-density lipoproteins (HDL).[8] HDL-associated PON1 has been frequently shown to have antioxidant and anti-inflammatory potential mainly by protecting lipids of HDLs and low-density lipoproteins from oxidative modifications.[9],[10]

In the skin, reduction in PON1 level in vitiligo patients revealed their role in ROS pathogenesis and the diminution of PON1 activity in OS.[11] Lower PON1 activity was also observed in the sera of psoriasis patients compared with healthy subjects, confirming that psoriasis is associated with OS, and impairment of the antioxidant system in the plasma of patients may play a role in pathogenesis and progression of psoriasis and related complications.[12]

In Alopecia areata (AA), there is a proved alteration in oxygen-free radical scavenging process manifested by decreases in lymphocytes and plasma total antioxidant status and erythrocytes GSH.[13] PON1 activity was found to be lowered in patient with AA, which may be related to an increase in oxidant and a decrease in antioxidant levels.[14]

The aim of our work is to estimate serum PON1 level in patients with AGA and correlate its levels with disease severity, which may help in determining if there is a role of ROS in the pathogenesis of AGA, and consequently, could help in the management of AGA by adding antioxidants in the treatment protocols.


   Subjects and Methods Top


This research work was designed as a case–control study at the outpatient clinic of Dermatology Department of Mansoura University Hospital, Mansoura, Egypt, during the period from December 2018 to June 2019. The study was approved by Institutional Research Board with approval code “MS.18.05.128.”

Subjects

The subjects were classified into two groups, Group I included 40 patients complaining of AGA, and Group II, that included 40 apparently healthy age- and sex-matched controls. All patients were below 50 years (as investigations reported a progressive decrease in PON1 activity in elderly subjects).[15] Patients included in the study were those with AGA who didnot use topical treatment or stopped it for at least 3 months before being enrolled. . Patients were excluded as follows: patients using systemic treatment such as steroids and immunosuppressive drugs that likely can cause regrowth of hair within the past 3 months, those with associated diseases that alter serum PON1 level as vitiligo, psoriasis, thyroid, liver, renal, cardiovascular diseases, diabetes, and other conditions that affect PON1 level as pregnancy, smoking, alcoholism, obesity.

A written informed consent was taken from all participants before the study. Full history taking includes personal history, history of present illness, previous medications, and the date of discontinuation, if any. Family history of AGA or other skin or systemic disease was recorded. General examination was done to exclude systemic diseases associated with hair loss. Clinical assessment of the degree of AGA according to Hamilton classification for clinical assessment of male pattern hair loss [Figure 1][16] and Ludwig classification for clinical assessment of female pattern hair loss [Figure 2].[17] Full dermoscopic examination using Dermlite 3 (3 Gen, USA) and the characteristic trichoscopic features of AGA were evaluated.
Figure 1: Hamilton–Norwood classification of male pattern hair loss 16

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Figure 2: Ludwig classification of hair loss among females 17

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Methods

Collection of blood samples

Five milliter of fasting (6–8 h) venous blood were collected from each subject participating in this study. Determination of serum (PON1) had been carried out using enzyme-linked immunosorbent assay kits supplied from Wuhan EIAab science CO., Ltd., with catalog no: E0243 h.

Data management and statistical analysis

The Statistical Package for the Social Science (Chicago: SPSS Inc) program version 17 was used for analysis of data. The data were summarized using descriptive statistics: mean, median, standard deviation (SD), minimal, and maximum values for quantitative variables and number and percentage for qualitative values. Statistical differences between groups were tested using Chi-square test for qualitative variables, independent sample t-test, and analysis of variance test for quantitative normally distributed variables. Simple linear correlation for quantitative data was also done. Value was considered weak if < 0.25, mild if >0.25−<0.5, moderate if >0.5−<0.75, and strong if >0.75.


   Results Top


Sociodemographic data

The present study was conducted on 40 cases with AGA, their mean age 34.2 years, they were 20 males (50%) and 20 females (50%) in addition to 40 healthy controls of matched age and gender. No significant differences were found in occupation between cases (data not shown).

Clinical assessment of androgenetic alopecia cases

AGA severity was assessed in all studied cases; 40% were mild, 37.5% were moderate, and 22.5% were severe cases. Mild cases included Grade I (according to Ludwig classification) and Grades I, II, III (according to Hamilton classification). Moderate cases included Grade II (according to Ludwig classification) and Grades IV and V (according to Hamilton classification). Severe cases included Grade III (according to Ludwig classification) and Grades VI and VII (according to Hamilton classification).

Comparison Paraoxonase 1 concentration between all studied groups

AGA cases showed significantly lower PON1 concentration when compared to control group (mean ± SD = 106.6 ± 31.5 versus 299.7 ± 71.9, respectively; P < 0.001) [Figure 3].
Figure 3: Paraoxonase 1 concentration in all studied groups

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Receiver operating characteristic curve of serum PON1 was conducted for discrimination between AGA cases and control groups. Excellent area under curve (AUC) was found (AUC = 0.974, P < 0.001). At cutoff value of 191, sensitivity was 92.5%, specificity was 100%, positive predicted value (PPV) was 100%, negative predicted value (NPV) was 87%, and accuracy was 95% [Figure 4].
Figure 4: Receiver operating characteristic curve of serum Paraoxonase 1 for discrimination between androgenetic alopecia cases and control group.

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No significant differences were found in PON1 level between gender, FH, onset in all AGA cases [Table 1]. Comparison of PON1 level between severity grades in all AGA cases showed that significantly lower PON1 level was associated with more severe grades in AGA patients [Table 2]. Using Pearson's correlation, PON1 showed significant negative correlation with severity (r = −0.541, P < 0.001). Otherwise, no significant correlations were found between PON1 level with other studied parameters in AGA cases (P > 0.05 for each) [Table 3].
Table 1: Comparison of paraoxonase level between gender, family history, disease onset in all androgenetic alopecia cases

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Table 2: Comparison of paraoxonase level between severity grades in all androgenetic alopecia cases

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Table 3: Correlation of paraoxonase level with other studied parameters in all androgenetic alopecia cases

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Prediction of androgenetic alopecia development and severity within healthy subjects

Logistic regression analysis was conducted for the prediction of AGA development within healthy subjects, using age, gender, and PON1 as covariates. Low PON1 level was considered as independent risk factor for the development of AGA [Table 4]. Ordinal regression analysis was conducted for the prediction of severity of AGA cases using age, gender, clinical data, and PON1 as covariates. Lower PON1 was the only predictor for higher severity in studied AGA patients [Table 5].
Table 4: Logistic regression analysis for prediction of androgenetic alopecia development within healthy subjects

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Table 5: Prediction of severity of androgenetic alopecia cases

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   Discussion Top


Being a widespread psychologically distressing disease,[1],[2] AGA pathogenesis has been the focus of different studies in the past years.[3],[4],[5],[6] The involvement of genetic, hormonal factors (androgens),[18] in addition to inflammation,[5],[6] was suggested. Histological studies confirmed the presence of perifollicular inflammation in the upper third[5],[6] together with OS in dermal papilla of the hair follicles the patients with AGA.[3],[6]

PON1 is an HDL-associated antioxidant enzyme capable of hydrolyzing lipid peroxides.[19] Previous studies have shown that the activity of PON1 in human serum is downregulated by OS.[20],[21] The current study was conducted to detect serum PON1 level in patients with AGA and correlate it with disease severity which may help to determine if there is a role of ROS in pathogenesis of AGA.

Several research groups have studied the relationship between OS and AGA. Prie et al. conducted a study to measure the several enzymes and products of OS in the blood of patients with AGA. They found a significantly decreased (P < 0.01) superoxide dismutase activity in patients with AGA compared to controls.[22] Another study by Kaya Erdogan et al. measured total oxidant levels (TOS), total antioxidant levels (TAS), and oxidative stress index (OSI). They found that TOS and OSI were significantly higher in patient group, but when TAS, TOS, and OSI levels were assessed according to AGA stage, there was no significant difference between groups.[23]

To the best of our knowledge, the relationship between serum PON1 and disease activity in AGA subjects has not been studied or published before. This explains that there are no previously reported results, in literature, to compare with our findings. Although it had been studied in other forms of hair loss, such as AA,[14],[24]

Regarding the prevalence and severity of AGA among the different age groups, different results have been reported, particularly in males. The present study was conducted on 40 cases with AGA, their mean age 34.2 years, they were 20 males (50%) and 20 females (50%) versus 40 healthy control group of matched age and gender. There is no statistically significant difference between the two groups in this respect.

First, according to Hamilton's study in 1951, by the age of 30, the mean prevalence was 30%, 40% in mid-forties, and this rate rose to 50% by the age of 50 in Caucasian men.[25] In a recent study from Turkey, these rates were, respectively, 71.1%, 77.2%, and 83.3%.[26] In studies from US, Italy, Norway, and Australia, similar results to Hamilton's study were reported.[27],[28],[29],[30] Birch et al. reported that the prevalence of female type AGA in women younger than 50 years was 6%, whereas in women older than 50 years was 52.6% in England.[31] Paik et al. found that the prevalence of AGA in Korea was 14.1% in men and 5.6% in women.[32]

We found that half of patients with AGA had positive family history, all patients had history of stress. None of them was smoker, had systemic disease, or received medications. AGA severity was assessed in all studied cases; 40% were mild, 37.5% were moderate, and 22.5% were severe cases. This came in agreement with Paik et al. who showed that among patients with AGA included in his study, 50% had a family history of AGA.[32] In the study conducted by Kaya Erdogan et al., family history in AGA was present in 66.7% (22 of 33 patients), and the Hamilton–Norwood scale was Stage 3 in 72.7% of patients and Stage 4 in 27.3%.[23]

In our study, the mean level of PON1 in the cases with AGA was statistically significant lower as compared with the control group. Furthermore, a significantly lower PON1 level was associated with more severe grades of AGA. Interestingly, the best cutoff of PON1 to differentiate between AGA and control was 191, with a sensitivity of 92.5%, specificity 100%, PPV was 100%, NPV was 87%, and accuracy was 95%, i.e. PON1 can be used as a predictor of AGA in the healthy.

In the study conducted by Bilgili et al., to investigate serum PON1 activity and oxidative status in subjects with AA, they showed that PON1 activity was significantly lower in the subjects with AA than controls (P = 0.001).[14] Dizen-Namdar et al. included 60 AA and 50 healthy control subjects to test serum PON1 in cases with AA. They showed that serum PON1 activities were significantly lower in the patients with AA compared to the control group (P < 0.001).[24] Putting in consideration that studies on the role of OS in AA have been preceding those carried out on AGA,[33],[34] it might be worthy to study, in depth, the role of OS in AGA, and hence, predict similar changes.


   Conclusion Top


This study is considered the first to investigate the PON1 enzyme level in subjects with AGA, our results revealed that the level of PON1 decreased significantly in most of cases with significant decrease in severe grades, and this may prove that OS is considered one of the aggravating factors of AGA, which in turn may help in the management of AGA by adding antioxidants in treatment.

Some limitations were encountered in this study, being a single-center study with a relatively small sample size. Furthermore, the study assessed the enzyme level in sera of AGA patients but not from tissue samples.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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