Characterization of a prolactin gene polymorphism and its associations with systemic lupus erythematosus.
OBJECTIVE
Hyperprolactinemia is associated with systemic lupus erythematosus (SLE), but the mechanism is unknown. Prolactin is expressed in T lymphocytes and is under the control of an alternative promoter region. We characterized a G/T single-nucleotide polymorphism (SNP) at position -1149 of this promoter and assessed its prevalence in patients with SLE.


METHODS
Electrophoretic mobility shift assays (EMSAs) were performed to determine DNA protein complex formation in the prolactin promoter. Transient transfection of reporter gene constructs containing the G/T promoter alleles into the Jurkat T cell line were used to determine transcription activity. Peripheral blood lymphocytes (PBLs) were treated in vitro with phytohemagglutinin (PHA) to determine levels of prolactin messenger RNA (mRNA).


RESULTS
EMSAs indicated that binding of a GATA-related transcription factor was altered by the G/T SNP at position -1149. Transient transfection studies in Jurkat cells showed that the G allele consistently produced higher promoter activity. PHA treatment of PBLs in vitro induced a greater increment of prolactin mRNA from patients with the GG(-1149) genotype than from those with the TT(-1149) genotype. Disease association studies in a cohort of SLE patients demonstrated an increased frequency of the prolactin -1149 G allele compared with control subjects.


CONCLUSIONS
We found a functionally significant polymorphism that alters prolactin promoter activity and mRNA levels in the lymphocytes. Altered local prolactin production by immune cells may contribute to disease progression by affecting T cell function.
Stevens
A
A
University of Manchester, UK.
Ray
D
D
Alansari
A
A
Hajeer
A
A
Thomson
W
W
Donn
R
R
Ollier
W E
WE
Worthington
J
J
Davis
J R
JR
D000483:Alleles; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000235:genetics*
D011388:Prolactin