Role of serum leptin levels and leptin receptor gene polymorphisms in systemic lupus erythematosus



Serum leptin and leptin receptor gene polymorphisms may play a role in the etiopathogenesis of SLE.


This study was undertaken to explore the relationship between serum leptin levels and leptin receptor (LEPR) gene polymorphisms with susceptibility to SLE in Egyptian population and to study their relationships with clinical, laboratory, radiographic findings, and disease activity of SLE (SLEDAI).

Materials and methods

A total of 50 unrelated female patients, who met the SLICC classification criteria for SLE and fifty healthy blood donors, matched for age, sex, and BMI with SLE patients, serving as a control group, were included in this study. All participants had completed preliminary questionnaires and clinical, laboratory, and radiographic examinations. Serum leptin levels were measured by ELISA assays. LEPR genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We compared serum leptin levels and LEPR gene polymorphisms in SLE patients and controls, and we tested their relationships with clinical, laboratory, and radiographic findings and SLEDAI in SLE patients.


The present study showed significant differences of serum leptin levels between SLE patients and controls (p < 0.001). Moreover, higher frequencies of variant genotype (AA) and (A) allele were found in SLE patients compared to controls (p = 0.008 and 0.001, respectively). No associations were observed between the serum leptin, various LEPR genotypes, and gene alleles and the development of clinical, laboratory, and radiological manifestations. Furthermore, no associations were observed between the various LEPR genotypes or gene alleles and leptin levels (p = 0.633 and 0.337 respectively) in SLE patients. Additionally, no correlations were observed between leptin levels, various genotypes, and alleles with SLEDAI (p = 0.244, 0.741, and 0.838 respectively) in SLE patients.


Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian population; however, they are not associated with the development of clinical, lab, and radiological findings. Disease activity is neither correlated with serum leptin level nor associated with LEPR gene polymorphism. Serum levels of leptin are not associated with LEPR gene polymorphism.

Key Points
Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian patients.
Serum leptin is not associated with SLE disease activity.

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  1. 1.

    Li H, Zhang T, Leng R, Li X, Li X, Pan H (2015) Plasma/serum leptin levels in patients with systemic lupus erythemaosus: a meta-analysis. Arch Med Res 46:551–556

    CAS  Article  Google Scholar 

  2. 2.

    Tsokos G (2011) Systemic lupus erythematosus. N Engl J Med 365:2110–2121

    CAS  Article  Google Scholar 

  3. 3.

    La Cava A (2016) Leptin-related polymorphisms and SLE. Inflamm Cell Signal 3:e1171

    Google Scholar 

  4. 4.

    Jeganathan V, Peeva E, Diamond B (2014) Hormonal milieu at time of B cell activation controls duration of autoantibody response. J Autoimmun 53:46–54

    CAS  Article  Google Scholar 

  5. 5.

    La Cava A, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4:371–379

    Article  Google Scholar 

  6. 6.

    Montague C, Farooqi I, Whitehead J, Soos M, Rau H, Wareham N et al (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908

    CAS  Article  Google Scholar 

  7. 7.

    Mantzoros C, Magkos F, Brinkoetter M, Sienkiewicz E, Dardeno T, Kim SY et al (2011) Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 301:E567–E584

    CAS  Article  Google Scholar 

  8. 8.

    Procaccini C, Jirillo E, Matarese G (2012) Leptin as an immunomodulator. Mol Asp Med 33:35–45

    CAS  Article  Google Scholar 

  9. 9.

    Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C et al (2010) Role of leptin in the activation of immune cells. Mediat Inflamm 568343

  10. 10.

    Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Obesity Society et al (2014) 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults:a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 63(25 Pt B):2985–3023

    Article  Google Scholar 

  11. 11.

    Amarilyo G, Iikuni N, Shi F, Liu A, Matarese G, La Cava A (2013) Leptin promotes lupus T-cell autoimmunity. Clin Immunol 149:530–533

    CAS  Article  Google Scholar 

  12. 12.

    Fujita Y, Fujii T, Mimori T, Sato T, Nakamura T, Iwao H, Nakajima A, Miki M, Sakai T, Kawanami T, Tanaka M, Masaki Y, Fukushima T, Okazaki T, Umehara H (2014) Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice. J Immunol 192:979–984

    CAS  Article  Google Scholar 

  13. 13.

    Stofkova A (2009) Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul 43:157–168

    CAS  PubMed  Google Scholar 

  14. 14.

    Zhao J, Wu H, Langefeld CD, Kaufman KM, Kelly JA, Bae SC, Marta E. Alarcón-Riquelme for the BIOLUPUS and GENLES networks, Alarcón GS, Anaya JM, Criswell LA, Freedman BI, Kamen DL, Gilkeson GS, Jacob CO, James JA, Merrill JT, Gaffney PM, Sivils KM, Niewold TB, Petri MA, Song ST, Jeong HJ, Ramsey-Goldman R, Reveille JD, Scofield RH, Stevens AM, Boackle SA, Vilá LM, Chang DM, Song YW, Vyse TJ, Harley JB, Brown EE, Edberg JC, Kimberly RP, Hahn BH, Grossman JM, Tsao BP, la Cava A (2015) Genetic associations of leptin-r elated polymorphisms with systemic lupus erythematosus. Clin Immunol 161:157–162

    CAS  Article  Google Scholar 

  15. 15.

    Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D, Mantzoros CS (2001) The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab 86:4434–4439

    CAS  Article  Google Scholar 

  16. 16.

    Sada KE, Yamasaki Y, Maruyama M, Sugiyama H, Yamamura M, Maeshima Y, Makino H (2006) Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus. J Rheumatol 33:1545–1552

    CAS  PubMed  Google Scholar 

  17. 17.

    Kim HA, Choi GS, Jeon JY, Yoon JM, Sung JM, Suh CH (2010) Leptin and ghrelin in Korean systemic lupus erythematosus. Lupus 19:170–174

    CAS  Article  Google Scholar 

  18. 18.

    Garcia-Gonzalez A, Gonzalez-Lopez L, Valera-Gonzalez IC, Cardona-Muñoz EG, Salazar-Paramo M, González-Ortiz M, Martínez-Abundis E, Gamez-Nava JI (2002) Serum leptin levels in women with systemic lupus erythematosus. Rheumatol Int 22:138–141

    Article  Google Scholar 

  19. 19.

    McMahon M, Skaggs BJ, Sahakian L, Grossman J, FitzGerald J, Ragavendra N, Charles-Schoeman C, Chernishof M, Gorn A, Witztum JL, Wong WK, Weisman M, Wallace DJ, la Cava A, Hahn BH (2011) High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids. Ann Rheum Dis 70(9):1619–1624

    CAS  Article  Google Scholar 

  20. 20.

    Lee YH, Nath SK (2005) Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet 118:434–443

    Article  Google Scholar 

  21. 21.

    Bentham J, Vyse TJ (2013) The development of genome-wide association studies and their application to complex diseases, including lupus. Lupus 22:1205–1213

    CAS  Article  Google Scholar 

  22. 22.

    Afroze D, Yousuf A, Ali R, Kawoosa F, Akhtar T, Reshi S, Shah ZA (2015) Serum leptin levels, leptin receptor gene (LEPR) polymorphism, and the risk of systemic lupus erythematosus in Kashmiri population. Immunol Investig 44:113–125

    CAS  Article  Google Scholar 

  23. 23.

    Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR et al (2012) Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686

    Article  Google Scholar 

  24. 24.

    Li HM, Zhang TP, Leng RX, Li XP, Wang DG, Li XM, Ye DQ, Pan HF (2017) Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population. J Cell Mol Med 21(9):1732–1741

    CAS  Article  Google Scholar 

  25. 25.

    Bencivelli W, Vitali C, Isenberg DA, Smolen JS, Snaith ML, Sciuto M et al (1992) Disease activity in systemic lupus erythematosus: report of the consensus study Group of the European Workshop for rheumatology research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 10(5):549–554

    CAS  PubMed  Google Scholar 

  26. 26.

    La Cava A, Alviggi C, Matarese G (2004) Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med (Berl) 82(1):4–11

    Article  Google Scholar 

  27. 27.

    Al M, Ng L, Tyrrell P, Bradley T, Silverman E (2009) Adipokines as novel biomarkers in paediatric systemic lupus erythematosus. Rheumatology 48:497–501

    CAS  Article  Google Scholar 

  28. 28.

    Vadacca M, Zardi EM, Margiotta D, Rigon A, Cacciapaglia F, Arcarese L, Buzzulini F, Amoroso A, Afeltra A (2013) Leptin, adiponectin and vascular stiffness parameters in women with systemic lupus erythematosus. Intern Emerg Med 8:705–712

    Article  Google Scholar 

  29. 29.

    Ma L, Li D, Sookha MR, Fang M, Guan Y, Sun X, Guan J (2015) Elevated serum leptin levels in patients with systemic lupus erythematosus. Pharmazie 70:720–723

    CAS  PubMed  Google Scholar 

  30. 30.

    Margiotta D, Navarini L, Vadacca M, Basta F, Lo Vullo M, Pignataro F, Zardi EM, Afeltra A (2016) Relationship between leptin and regulatory T cells in systemic lupus erythematosus: preliminary results. Eur Rev Med Pharmacol Sci 20:636–641

    CAS  PubMed  Google Scholar 

  31. 31.

    Wang LH, Liu YC, Wang JH, Lee CJ, Hsu BG (2017) Serum leptin level positively correlates with metabolic syndrome among elderly Taiwanese. Ci Ji Yi Xue Za Zhi 29(3):159–164

    PubMed  Google Scholar 

  32. 32.

    Lee YH, Song GG (2018) Association between circulating leptin levels and systemic lupus erythematosus: an updated meta-analysis. Lupus 27(3):428–435

    CAS  Article  Google Scholar 

  33. 33.

    Wisłowska M, Rok M, Stepień K, Kuklo-Kowalska A (2008) Serum leptin in systemic lupus erythematosus. Rheumatol Int 28:467–473

    Article  Google Scholar 

  34. 34.

    Li HM, Zhang TP, Leng RX, Li XP, Li XM, Pan HF (2015) Plasma/serum leptin levels in patients with systemic lupus erythematosus: a meta-analysis. Arch Med Res 46:551–556

    CAS  Article  Google Scholar 

  35. 35.

    De Sanctis JB, Zabaleta M, Bianco NE, Garmendia JV, Rivas L (2009) Serum adipokine levels in patients with systemic lupus erythematosus. Autoimmunity 42(4):272–274

    Article  Google Scholar 

  36. 36.

    Méndez-Sánchez N, Bermejo-Martínez L, Chávez-Tapia NC, Zamora-Valdés D, Sánchez-Lara K, Uribe-Ramos MH, Ponciano-Rodríguez G, Baptista-González HA, Ramos MH, Uribe M (2006) Obesity-related leptin receptor polymorphisms and gallstones disease. Ann Hepatol 5:97–102

    Article  Google Scholar 

  37. 37.

    Chia VM, Newcomb PA, Lampe JW, White E, Mandelson MT, McTiernan A, Potter JD (2007) Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomark Prev 16:2697–2703

    CAS  Article  Google Scholar 

  38. 38.

    Khatoon K, Arkani M, Safaei A (2011) Association of leptin receptor gene Gln223Arg polymorphism with susceptibility to colorectal cancer. Gastroenterol Hepatol Bed Bench 4:92–198

    Google Scholar 

  39. 39.

    Carrillo-Vazquez JP, Lopez-Alcantar J, Chimal-Vega B et al (2013) G-2548A Lepin promoter and Q223R lepin receptor polymorphism in obese Mexican subjects. Am J Agric Biol Sci 8(1):34–43

    CAS  Article  Google Scholar 

  40. 40.

    Barbosa VDS, Francescantônio PL, Silva NAD (2015) Leptina e adiponectina no lúpus eritematoso sistêmico: correlações clínicas e laboratoriais. Rev Bras Reumatol 55:140–145

    Article  Google Scholar 

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Corresponding author

Correspondence to Reham M. Shaat.

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The study was approved by the local ethical committee code MS/16.06.92.



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Afifi, A.EM.A., Shaat, R.M., Gharbia, O.M. et al. Role of serum leptin levels and leptin receptor gene polymorphisms in systemic lupus erythematosus. Clin Rheumatol 39, 3465–3472 (2020).

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  • Egyptian
  • Leptin
  • Leptin receptor gene polymorphism
  • Systemic lupus erythematosus