Polymorphisms of the human prolactin gene - implications for production oflymphocyte prolactin and systemic lupus erythematosus

Hyperprolactinaemia is associated with systemic lupus erythematosus (SLE) b ut the mechanism is unknown. Prolactin is expressed not only by pituitary l actotrophic cells but also by T-lymphocytes under the control of an alterna tive upstream promoter region. T-lymphocytes from SLE patients have been sh own to secrete more prolactin than controls, thus implying a possible under lying difference in regulation. This may be due to genetic polymorphism tha t can be determined by scanning for mutations and using a variety of method s to determine their function. A polymorphism may also be used in disease a ssociation studies as it may be in linkage disequilibrium with a disease ge ne on the same haplotype. Single nucleotide polymorphisms (SNPs) have been found across the prolactin gene region including the extrapituitary and the pituitary promoter regions. These SNPs have been examined for genetic asso ciation with SLE and potential effects upon the function of the gene, One SNP in the lymphocyte specific upstream promoter affects prolactin tran scription and disease association studies in a cohort of SLE cases demonstr ated an increased frequency of the PRL-(1149) G allele compared to control subjects. This indicates a possible mechanism for the association of prolac tin with SLE. Although prolactin is likely to be one of several predisposin g factors in the pathogenesis and progression of SLE, this suggests that ma nipulation of lymphocyte prolactin production (rather than pituitary produc tion) might be a useful therapeutic approach.