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vol. 14
Clinical research

Association of extrapituitary prolactin promoter polymorphism with disease susceptibility and anti-RNP antibodies in Mexican patients with systemic lupus erythematosus

Jorge Hernández-Bello, Claudia A. Palafox-Sanchez, Samuel García-Arellano, Zyanya Reyes-Castillo, Ana L. Pereira-Suárez, Isela Parra-Rojas, José E. Navarro-Zarza, Ulises De la cruz-Mosso, Nora M. Torres-Carrillo, José Francisco Muñoz-Valle

Arch Med Sci 2018; 14, 5: 1025–1032
Online publish date: 2016/09/02
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Prolactin (PRL) is a 23-kDa protein that can be synthesized and secreted by pituitary and extrapituitary tissues such as immune cells due to its expression being regulated by two independent promoter regions. The promoter which is responsible for extrapituitary expression contains the single nucleotide polymorphism (SNP) –1149 G/T previously associated with autoimmune diseases in various populations. This study evaluates the relationship of PRL –1149 G/T polymorphism with PRL serum levels and clinical characteristics in systemic lupus erythematosus (SLE) patients from western Mexico.

Material and methods
One hundred and sixty-three SLE patients classified according to the 1982 American College of Rheumatology (ACR) SLE classification criteria and 326 unrelated control subjects (CS), both from western Mexico, were included. The PRL –1149 G/T polymorphism was genotyped using the polymerase chain reaction restriction fragment length polymorphism technique, and both PRL serum levels and autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA).

We found an association between the PRL –1149 TT genotype and SLE according to the recessive genetic model (OR = 2.26, 95% CI: 1.01–5.08, p = 0.04). The TT genotype was associated with anti-RNP antibodies (p = 0.04) and with higher scores of the Mex-SLEDAI (p = 0.02). Moreover, SLE patients showed elevated PRL serum levels (12.4 ng/ml; p < 0.01), and this condition was associated with renal activity and the presence of anti-RNP antibodies.

PRL –1149 TT genotype is associated with susceptibility to SLE in a Mexican-Mestizo population, and high PRL serum levels are associated with anti-RNP antibodies and renal activity.


systemic lupus erythematosus, prolactin, genetic polymorphism, autoimmunity, anti-RNP antibodies

Koutsokeras T, Healy T. Systemic lupus erythematosus and lupus nephritis. Nat Rev Drug Discov 2014; 13: 173-4.
Tsokos GC. Systemic lupus erythematosus. N Engl J Med 2011; 365: 2110-21.
Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2002; 16: 847-58.
Reyes-Castillo Z, Pereira-Suárez AL, Palafox-Sanchez CA, et al. The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population. Gene 2013; 525: 130-5.
Marano RJ, Ben-Jonathan N. Minireview: extrapituitary prolactin: an update on the distribution, regulation, and functions. Mol Endocrinol 2014; 28: 622-33.
Beda-Maluga K, Pisarek H, Romanowska I, Komorowski J, Świętosławski J, Winczyk K. Ultrafiltration – an alternative method to polyethylene glycol precipitation for macroprolactin detection. Arch Med Sci 2015; 11: 1001-7.
Orbach H, Zandman-Goddard G, Boaz M, et al. Prolactin and autoimmunity: hyperprolactinemia correlates with serositis and anemia in SLE patients. Clin Rev Allergy Immunol 2012; 42: 189-98.
Stevens A, Ray D, Alansari A, et al. Characterization of a prolactin gene polymorphism and its associations with systemic lupus erythematosus. Arthritis Rheum 2001; 44: 2358-66.
Harvey S, Arámburo C, Sanders EJ. Extrapituitary production of anterior pituitary hormones: an overview. Endocrine 2012; 41: 19-30.
Jara LJ, Vera-Lastra O, Miranda JM, Alcala M, Alvarez-Nemegyei J. Prolactin in human systemic lupus erythematosus. Lupus 2001; 10: 748-56.
Pacilio M, Migliaresi S, Meli R, Ambrosone L, Bigliardo B, Di Carlo R. Elevated bioactive prolactin levels in systemic lupus erythematosus: association with disease activity. J Rheumatol 2001; 28: 2216-21.
Jacobi AM, Rohde W, Ventz M, Riemekasten G, Burmester GR, Hiepe F. Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity. Lupus 2001; 10: 554-61.
Karimifar M, Tahmasebi A, Bonakdar ZS, Purajam S. Correlation of serum prolactin levels and disease activity in systematic lupus erythematosus. Rheumatol Int 2013; 33: 511-6.
Cc M, Cs L, Sc T. Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients. Br J Rheumatol 1997; 36: 986-9.
Orbach H, Shoenfeld Y. Hyperprolactinemia and autoimmune diseases. Autoimmun Rev 2007; 6: 537-42.
Ignacak A, Kasztelnik M, Sliwa T, Korbut RA, Rajda K, Guzik TJ. Prolactin – not only lactotrophin. A “new” view of the “old” hormone. J Physiol Pharmacol Off J Pol Physiol Soc 2012; 63: 435-43.
Gerlo S, Davis JRE, Mager DL, Kooijman R. Prolactin in man: a tale of two promoters. BioEssays News Rev Mol Cell Dev Biol 2006; 28: 1051-5.
Montoya-Díaz E, Cervera-Castillo H, Chávez-Sánchez L, et al. Prolactin promoter polymorphism (-1149 G/T) is associated with anti-DNA antibodies in Mexican patients with systemic lupus erythematosus. Immunol Invest 2011; 40: 614-26.
Fojtíková M, Cerná M, Cejková P, Ruzicková S, Dostál C. Extrapituitary prolactin promoter polymorphism in Czech patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis 2007; 66: 706-7.
Mellai M, Giordano M, D’Alfonso S, et al. Prolactin and prolactin receptor gene polymorphisms in multiple sclerosis and systemic lupus erythematosus. Hum Immunol 2003; 64: 274-84.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39: 363-9.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
Reyes-Castillo Z, Palafox-Sánchez CA, Parra-Rojas I, et al. Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features. Clin Exp Immunol 2015; 182: 119-31.
Lewis CM. Genetic association studies: design, analysis and interpretation. Brief Bioinform 2002; 3: 146-53.
Stolfa J, Fojtíková M, Cejková P, Cerná M, Sedová L, Dostál C. Polymorphism of the prolactin extrapituitary promoter in psoriatic arthritis. Rheumatol Int 2007; 27: 1095-6.
Fojtíková M, Cejková P, Bečvář R, Vencovský J, Tomasová Studýnková J, Cerná M. Polymorphism of the extrapituitary prolactin promoter and systemic sclerosis. Rheumatol Int 2010; 30: 1691-3.
Rangel-Villalobos H, Muñoz-Valle JF, González-Martín A, Gorostiza A, Magaña MT, Páez-Riberos LA. Genetic admixture, relatedness, and structure patterns among Mexican populations revealed by the Y-chromosome. Am J Phys Anthropol 2008; 135: 448-61.
Trifunović J, Miller L, Debeljak Ž, Horvat V. Pathologic patterns of interleukin 10 expression – a review. Biochem Med 2015; 25: 36-48.
Jimena P, Aguirre MA, López-Curbelo A, de Andrés M, Garcia-Courtay C, Cuadrado MJ. Prolactin levels in patients with systemic lupus erythematosus: a case controlled study. Lupus 1998; 7: 383-6.
Moszkorzová L, Lacinová Z, Marek J, Musilová L, Dohnalová A, Dostál C. Hyperprolactinaemia in patients with systemic lupus erythematosus. Clin Exp Rheumatol 2002; 20: 807-12.
Vekemans M, Robyn C. Influence of age on serum prolactin levels in women and men. Br Med J 1975; 4: 738-9.
Legorreta-Haquet MV, Flores-Fernández R, Blanco-Favela F, et al. Prolactin levels correlate with abnormal B cell maturation in MRL and MRL/lpr mouse models of systemic lupus erythematosus-like disease. Clin Develop Immunol 2013; 2013: 287469.
Vera-Lastra O, Mendez C, Jara LJ, et al. Correlation of prolactin serum concentrations with clinical activity and remission in patients with systemic lupus erythematosus. Effect of conventional treatment. J Rheumatol 2003; 30: 2140-6.
Hooghe R, Dogusan Z, Martens N, Velkeniers B, Hooghe-Peters EL. Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus. Lupus 2001; 10: 719-27.
Miranda JM, Prieto RE, Paniagua R, et al. Clinical significance of serum and urine prolactin levels in lupus glomerulonephritis. Lupus 1998; 7: 387-91.
Peterson E, Robertson AD, Emlen W. Serum and urinary interleukin-6 in systemic lupus erythematosus. Lupus 1996; 5: 571-5.
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