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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 2  |  Page : 424-428

Leptin and metabolic syndrome in alopecia areata


1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Shebin Elkim, Egypt
2 Damnhour Medical National Institute, The General Organization for Teaching Hospitals and Institutes, Damanhour, Egypt
3 Department of Medical Biochemistry and Molecular Bioligy, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt

Date of Submission20-Sep-2021
Date of Decision19-Dec-2021
Date of Acceptance26-Dec-2021
Date of Web Publication27-Jul-2022

Correspondence Address:
Yasmine Gamal
Department of Dermatology, Andrology and STDs, MBBCh, Damnhour
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_175_21

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  Abstract 


Objectives
The aim of the study was to assess the role of leptin gene polymorphism in alopecia areata with metabolic syndrome (MS).
Background
Alopecia areata is considered an organ-specific autoimmune disease of hair follicles. Leptin, an adipocyte-derived hormone, represents a link between metabolism, nutritional status, and immune response. T helper1-promoting effects of leptin have been linked to develop experimentally induced autoimmune disease.
Patients and methods
This cross-sectional study was carried out on 50 alopecia areata with MS patients. Body mass index, Severity of Alopecia Tool score, blood pressure, serum fasting glucose, triglyceride, and leptin polymerase chain reaction were done for alopecia areata patients.
Results
In this cross-sectional study, the males represent 54% (27) and females 46% (23), their age ranging from 30 to 48 years with mean ± SD 36.7 ± 4.93. In all, 80% had sudden onset and 20% had gradual onset; 54% had progressive course of the disease; And 10% had positive family history. Patchy type was present in all cases. Regarding leptin gene polymorphism, GG genotype was present in 54% of patients. GA and alopecia areata were present in 30 and 16% of patients, respectively. No significant relation between leptin gene polymorphism and demographic and clinical data of alopecia areata with MS patients (P > 0.05) was found except for family history.
Conclusions
The study showed significant association between leptin gene polymorphism and susceptibility to alopecia areata with MS patients and ascertained that this polymorphism has a direct relationship with the severity of the disease.

Keywords: alopecia aerate, leptin, metabolic syndrome


How to cite this article:
Bazid HA, Hammam MA, Gamal Y, El Gayed EM. Leptin and metabolic syndrome in alopecia areata. Menoufia Med J 2022;35:424-8

How to cite this URL:
Bazid HA, Hammam MA, Gamal Y, El Gayed EM. Leptin and metabolic syndrome in alopecia areata. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:424-8. Available from: http://www.mmj.eg.net/text.asp?2022/35/2/424/352134




  Introduction Top


Alopecia areata (AA) is an autoimmune disease characterized by targeting of the hair follicle. Clinically, patients exhibit nonscarring hair loss with varying presentations across all age groups[1].

Hair growth and maintenance depends on three phases of hair cycle, anagen (active growth phase), catagen (involution phase), and telogen (resting phase). The type and length of the hair depends on the anagen phase. In normal healthy individuals, hair sheds out after the resting phase when the new hair anagen growth starts (exogen). In alopecias, hair shedding occurs even before the anagen starts leaving the hair follicle empty (kenogen). Thus, AA is generally a disorder of hair cycling and is considered to be a state of kenogen[1].

Historically, numerous hypotheses on the cause of AA have been proposed, such as infection, a trophoneurotic hypothesis, and hormonal fluctuations. The involvement of the immune system in the pathogenesis of AA has been recognized as the primary underlying cause[2].

Leptin is a 16-kD hormone or cytokine predominantly synthesized and secreted by adipocytes. Subcutaneous and visceral fat is the primary source of this protein encoded by the obese (ob) gene. Leptin is regarded as one of the main endogenous regulators of body weight and energy metabolism. Leptin secretion is positively correlated with body mass, and therefore, obesity is accompanied with high circulating leptin levels[3].

Leptin is a crucial factor for metabolic syndrome (MS) that is characterized by obesity, insulin resistance, hypertension, and dyslipidemia. Recent studies have suggested that the adipocyte-derived hormone leptin may have an important role in obesity and MS[4].

Leptin stimulates neutrophil chemotaxis and promotes macrophage phagocytosis, as well as production of pro-inflammatory cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor-α. Recently, it has also been shown that leptin acts as a negative signal for the proliferation of regulatory T cells, while stimulating T helper1 (Th1) cells[5].

Th1-promoting effects of leptin have been linked with clarity to an enhanced susceptibility to develop experimentally induced autoimmune disease[6].

The aim of this work was to assess the role of leptin gene polymorphism in AA with MS.


  Patients and methods Top


This cross-sectional study was carried out on 50 AA with MS patients. They were selected from Outpatient Clinic of Dermatology in Menoufia University Hospital spanning the period between June 2020 to December 2020.

A written informed consent according to Menofuia ethical committee that was in accordance with Helsinki Declaration in 1975 was obtained from patients after the procedure had been fully explained. Patients included in this study suffered from AAwith MS. Each patient was subjected to complete history taking and general and dermatological examinations. Alopecia areata Tool Score (SALT score) was done for all patients to assess the severity of the disease[7] Body mass index, blood pressure, serum fasting glucose, triglyceride, and leptin polymerase chain reaction (PCR) were done to AA patients.

Biochemical analysis

After 12 h overnight fasting, 5 ml of venous blood were taken from every subject by using sterile vein puncture under complete aseptic condition and distributed into three tubes as follow: 2 ml were put into EDTA tube for DNA extraction and genotyping of leptin gene (rs2167270) using the taqman allelic discrimination assay technique (real-time PCR); 1 ml of blood was put into sodium fluoride tube for measuring fasting blood glucose that was estimated by enzymatic colorimetric test, using the Spinreact kit, Ctra. Sta. Coloma, Spain[8].

Finally, the remaining 2 ml were transferred slowly into a plain tube. Samples were allowed to clot for 30 min before centrifugation for 15 min at approximately 3000 rpm. Serum was separated and kept frozen in aliquots at −80°C until use and avoid repeated freeze–thaw cycles for measuring triglycerides. Triglycerides were determined by enzymatic colorimetric test, using the Spinreact kit, Ctra. Sta. Coloma, Spain[9].

Body weight in kilograms and height in meters were obtained and body mass index was calculated as body weight divided by height in meters squared.

Detection of leptin gene (rs2167270) was performed by the TaqMan ® Allelic Discrimination assay (real-time PCR).

Two-ml blood was collected into EDTA containing tube for DNA extraction from the whole blood. Genomic DNA was extracted from frozen EDTA-treated blood sample using Gene JET™ Whole Blood Genomic DNA Purification Mini Kit (Thermo Fisher Scientific Inc., EU/Lithuania Waltham, Massachusetts, United States).

Leptin gene (rs2167270) polymorphism was genotyped using allelic discrimination assay by real-time PCR technique using TaqMan probe Waltham, Massachusetts, United States, Applied Biosystems, USA.

The maxima probe qPCR Master Mix (40X), primers and probes were supplied from Thermo Fisher Scientific; the probe sequence labeled with VIC and FAM fluorescent dyes was as follows: forward primer was 5'-GAGCCCCGTAGGAATCGCAGCGCCA-3' and the reverse primer was 5'-CGGTTGCAAGGTAAGGCC CCGGCGC-3'.

In all, 10 μl of master mix was added to 1.25 μl of the genotyping assay of primer/probe mix and 3.75 μl of DNAase-free water. Also, 5 μl of genomic DNA extract for every sample and 5 μl of DNAase-free water for the negative control reaction were applied. The following cycling conditions were used: initial denaturation was done at 95°C for 10 min, followed by 40 cycles of denaturation at 94°C for 15 s, primer annealing at 50°C for 60 s then extension at 72°C for 2 min and the last extension at 72°C for 1 min Analysis of data was completed using 7500 Real-Time PCR instrument, version 2.0.1, Applied Biosystems.

Statistical analysis

The statistical analysis was conducted using Statistical Package for Social Science (SPSS) version 20 on IBM compatible computer (SPSS Inc., Chicago, Illinois, USA). Qualitative data were expressed as number and percentage. Quantitative data were expressed as: arithmetic mean (X), standard deviation (SD), percentage (%), and median. χ2test and Spearman's exact test were used for comparing quantitative variables. Mann–Whitney U test (U test) was used in comparing two nonparametric quantitative variables. Kruskal–Wallis test was used for testing equality of population medians among groups as it is an extension of the Mann–Whitney test. Analysis of variance was used for comparison between three or more quantitative variables. The results were considered statically significant for P value greater than or equal to 0.001.


  Results Top


In this cross-sectional study of AA patients with MS, the males represent 54% (27) and females 46% (23), and the age ranged from 30 to48 years with Mean ± SD 36.7 ± 4.93. Also, 80% had sudden onset and 20% had gradual onset; 54% had progressive course of the disease;. and10% had positive family history. Patchy type was present in all cases. Regarding leptin gene polymorphism, GG genotype was present in 54% of patients. GA and AA were present in 30 and 16% of patients, respectively. No significant relation between leptin gene polymorphism and demographic and clinical data of AA with MS patients (P > 0.05) was found except for family history. Dermatographic data are shown in [Table 1].
Table 1: Dermographic data

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Males represent 54% (27) and female 46% (23), and their age ranged from 30 to 48 years with mean ± SD 36.7 ± 4.93. Clinical data of the studied cases are shown in [Table 2].
Table 2: Clinical data of the studied cases

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Eighty percent had sudden onset and 20% had gradual onset. Also, 54% had progressive course of the disease and 10% had positive family history. Patchy type was present in all cases. AA with MS regarding leptin gene polymorphism (N = 50) is shown in [Table 3].
Table 3: Alopecia areata with MS regarding leptin gene polymorphism (N=150)

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Regarding leptin gene polymorphism, GG genotype was present in 54% of patients. GA and AA were present in 30 and 16% of patients, respectively. Relation between leptin gene polymorphism and demographic and clinical data of AA with MS patients (N = 50) are shown in [Table 4].
Table 4: Relation between leptin gene polymorphism and demographic and clinical data of alopecia areata with MS patients (N=50)

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No significant relation between leptin gene polymorphism and demographic and clinical data of AA with MS patients (P > 0.05) was found except for family history.


  Discussion Top


AA is a common, nonscarring alopecia that affects 0.1–0.2% of the general population[10].

The etiology of AA is not exactly known. Among the many factors that have been under investigation, genetic constitution as well as nonspecific immune and organ-specific autoimmune reactions have been the main areas of concentration. There are other proposed origins reported, including infectious agents, cytokines, emotional stress, intrinsically abnormal melanocytes or keratinocytes, and neurologic factors[11].

Leptin is a 16-kD hormone predominantly synthesized and secreted by adipocytes. Leptin is regarded as one of the main endogenous regulators of body weight and energy metabolism. Leptin secretion is positively correlated with body mass and therefore obesity, insulin resistance, and MS are accompanied with high circulating leptin levels[3].

Leptin has a dual role as a hormone and as a cytokine. As a hormone, it influences multiple endocrine functions and bone metabolism. As a cytokine, leptin promotes inflammatory responses[12].

Upon leptin stimulation, dendritic cells exhibit increased production of multiple cytokines including IL-1, IL-6, IL-12, tumor necrosis factor-α, and macrophage inflammatory protein-1α and induces the expression of surface molecules, such as CD1a, CD80, CD83, or CD86[13].

IL-17-producing Th cells (Th17) have a crucial role in the promotion and maintenance of inflammatory and autoimmune pathologies. Leptin was demonstrated to increase Th17 population and responsiveness[14].

In AA also, there is a strong indication that CD4 and CD8 T cells are directly involved in the hair loss promotion mechanism[15].

Infiltrates of T helper (Th) cells, cytolytic T cells, natural killer cells, and plasmacytoid dendritic cells surround the lower part of the hair bulb during the anagen, the growth phase, where their autoimmune activities cause the collapse of the hair follicle immune privilege and alopecia. CD8+ cells recruit early in the disease and are thought to be the main cell type that initiates AA[16].

Autoreactive Th1, Th17, natural killer, and CD8+ cells produce interferon-γ, which disturbs functioning of the hair follicle and causes disruption of the hair growth cycle, premature hair loss, and inhibition of hair growth[2].

The current study was carried out on 50 AA with MS. Males represent 54% (27) and females 46% (23), and the age ranged from 30 to 48 years with mean ± SD 36.7 ± 4.93. In all, 80% had sudden onset and 20% had gradual onset; 54% had progressive course of the disease; and 10% had positive family history. Patchy type was present in all cases. Regarding leptin gene polymorphism, GG genotype was present in 54% of patients. GA and AA were present in 30 and 16% of patients, respectively.

To our knowledge, no available studies in literature has documented results similar to these results. But in line with our result, Serarslan et al.[17], reported in their study on AA patients that serum leptin and adiponectin levels were significantly higher in AA. Also, Yun et al.[4], demonstrated in their study that serum leptin was associated with MS in the adult Korean population and Li et al.[18] demonstrated that the levels of leptin was increased with the number of positive MS components.

In the study by Abdel Hay and Rashed[19], LEP G-2548A polymorphism was suggested to be a predictor for higher plasma leptin and increased risk of psoriasis and could be used as a marker for psoriasis-related comorbidity risk. They also carried out analysis of G-2548A polymorphism of the LEP gene and factors affecting plasma leptin levels in psoriasis and compared patients with and without MS.

Banihani et al.[20] in their study found asignificant association between rs2167270 leptin gene polymorphism and the incidence of atopic dermatitis (P < 0.05). The GG allele was more frequently associated with patients, compared to the AA and AG alleles.

The study by Afroze et al.[21] conducted on 100 systemic lupus erythematosus cases implicates a significant role of LEPR Q223R polymorphism and leptin levels in the development of systemic lupus erythematosus and its clinical manifestations.

In the current study, there is a significant relation between leptin gene polymorphism and family history, which, similar to Özdemir et al.[22], found a positive correlation between serum leptin and family history of psoratic patients.

The current study revealed that leptin gene polymorphism could be a predictor for increasing incidence and risk of AA in MS patients.


  Conclusion Top


The study showed a significant association between leptin gene polymorphism and susceptibility to AA with MS patients and ascertained that this polymorphism has a direct relationship with the severity of the disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Yun JE, Kimm H, Jo J, Jee SH. Serum leptin is associated with metabolic syndrome in obese and nonobese Korean populations. Metabolism 2010; 59:424–429.  Back to cited text no. 4
    
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Olsen EA, Hordinsky MK, Price VH, Roberts JL, Shapiro J, Canfield D, et al. Alopecia areata investigational assessment guidelines–Part II. J Am Acad Dermatol 2004; 51:440–447.  Back to cited text no. 7
    
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Maurya R, Bhattacharya P, Dey R, Nakhasi HL. Leptin functions in infectious diseases. Front Immunol 2018; 9:2741.  Back to cited text no. 13
    
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Reis BS, Lee K, Fanok MH, Mascaraque C, Amoury M, Cohn LB, et al. Leptin receptor signaling in T cells is required for Th17 differentiation. J Immunol 2015; 194:5253–5260.  Back to cited text no. 14
    
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Guo H, Cheng Y, Shapiro J, McElwee K. The role of lymphocytes in the development and treatment of alopecia areata. Expert Rev Clin Immunol 2015; 11:1335–1351.  Back to cited text no. 15
    
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Pratt CH, King LE, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers 2017; 3:1–7.  Back to cited text no. 16
    
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Serarslan G, Özcan O, Okyay E, Ünlü B, Karadağ M. Role of adiponectin and leptin in patients with alopecia areata with scalp hair loss. Irish J Med Sci 2021; 190:1015–1020.  Back to cited text no. 17
    
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Li G, Xu L, Zhao Y, Li L, Fu J, Zhang Q, et al. Leptin-adiponectin imbalance as a marker of metabolic syndrome among Chinese children and adolescents: the BCAMS study. PLoS ONE 2017; 12:e0186222.  Back to cited text no. 18
    
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Abdel Hay RM, Rashed LA. Association between the leptin gene 2548G/A polymorphism, the plasma leptin and the metabolic syndrome with psoriasis. Exp Dermatol 2011; 20:715–719.  Back to cited text no. 19
    
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Banihani SA, Elmadhoun RA, Khabour OF, Alzoubi KH. The rs2167270 polymorphism of leptin gene is associated with atopic dermatitis. Dermatoendocrinology 2018; 10:e1454191.  Back to cited text no. 20
    
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Afroze D, Yousuf A, Ali R, Kawoosa F, Akhtar T, Reshi S, et al. Serum leptin levels, leptin receptor gene (LEPR) polymorphism, and the risk of systemic lupus erythematosus in Kashmiri population. Immunol Invest 2015; 44:113–125.  Back to cited text no. 21
    
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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