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

Abstract

Introduction: 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).

Results: 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.

Conclusions: 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.

Keywords: anti-RNP antibodies; autoimmunity; genetic polymorphism; prolactin; systemic lupus erythematosus.

Figure 1

Serum levels by study groups and correlation of PRL levels with clinical characteristics in SLE. A – Prolactin serum levels in SLE patients and CS; B – prolactin serum levels in SLE according to duration of disease; C – prolactin serum levels in SLE according to anti-RNP seropositivity; D – prolactin serum levels in SLE according to renal activity. Numbers indicate median values. Boxes show 25–75% data ranges, whiskers show 5–95% ranges, and circles show outliers outside the 5–95% ranges. Statistical analysis was performed using the Mann-Whitney U test

Figure 2

Prolactin (PRL) serum levels from SLE patients according to Mex-SLEDAI score. Data provided as median (p25–p75). The three groups of patients had similar disease duration to avoid our results being affected by this variable. Statistical analysis was performed using the Kruskal-Wallis test NS – not significant, p-value > 0.05.

Figure 3

Prolactin serum levels by –1149 G/T PRL genotypes according to a dominant genetic model. Data provided as median (p25–p75). Statistical analysis was performed using the Mann-Whitney U test NS – not significant, p-value > 0.05, CS – control subjects, SLE – systemic lupus erythematosus