G allele of the SNP -1149G/T of the Extrapituitary prolactin promoter is involved in the SLE pathogenesis

Abstract

Objective Prolactin (PRL) is a polypeptide hormone produced by pituitary lactotrophs and extrapituitary tissues including immune cells. PRL acts as a cytokine and influences immune cells maturation and differentiation. Association between high serum PRL levels and systemic lupus erythematosus (SLE) has been demonstrated. Extrapituitary PRL synthesis is directed by an alternative promoter, which contains single nucleotide polymorphism (SNP) -1149 G/T. Higher PRL mRNA expression in lymphocytes has been associated with G allele. We investigated the role of this G allele in relation to clinical and laboratory features of SLE. Methods We investigated -1149 G/T SNP in 156 SLE patients and 123 healthy individuals (control group). SLE patients: 134 (85.9%) females and 22 (14.1%) males, average age 43.4 years. Control group: 40 (32.5%) females and 83 (67.5%) males, average age 38.7. PCR-RFLP methodology was used for -1149 G/T SNP detection. PCR: The 137 base pairs (bp) region of the PRL extrapituitary promoter was amplified by employing the following primers: forward 5’-GCAGGTCAAGATAACCTGGA and reverse 5’-CATCTCAGAGTTGAATTTATTTCCTT. RFLP: ApoI restriction endonucleasis was used. The genotypes we identified were:TT homozygote characterized by 120bp+17bp, GG homozygote by 85bp+35bp+17 bp and GT heterozygote by 120bp+85bp+35bp+17bp DNA fragments. Results were evaluated by χ 2 test with Bonferroni correction. Results In the SLE group there was no difference in genotype and allele frequencies compared to healthy individuals. With respect to specific organ manifestation of SLE we detected an association between G allele and arthritis (Pc=0.0086;OR 2.56,CI 1.51-4.33). According to age when SLE was diagnosed we observed GG genotype frequency in 21-to-40-years subgroup in 44.8% compared to 15.8% and 24.0% in the <20 years and >40 years subgroup, respectively (Pc=0.023;OR 2.94,CI 1.43-5.96). Conclusion The presence of G allele and GG genotype of the PRL extrapituitary promoter -1149 G/T SNP is associated with certain clinical features of SLE namely arthritis and age of SLE onset.