Polymorphisms of the human prolactin gene--implications for production of lymphocyte prolactin and systemic lupus erythematosus.
Hyperprolactinaemia is associated with systemic lupus erythematosus (SLE) but the mechanism is unknown. Prolactin is expressed not only by pituitary lactotrophic cells but also by T-lymphocytes under the control of an alternative upstream promoter region. T-lymphocytes from SLE patients have been shown to secrete more prolactin than controls, thus implying a possible underlying difference in regulation. This may be due to genetic polymorphism that can be determined by scanning for mutations and using a variety of methods to determine their function. A polymorphism may also be used in disease association studies as it may be in linkage disequilibrium with a disease gene 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 association with SLE and potential effects upon the function of the gene. One SNP in the lymphocyte specific upstream promoter affects prolactin transcription and disease association studies in a cohort of SLE cases demonstrated an increased frequency of the PRL-1149 G allele compared to control subjects. This indicates a possible mechanism for the association of prolactin with SLE. Although prolactin is likely to be one of several predisposing factors in the pathogenesis and progression of SLE, this suggests that manipulation of lymphocyte prolactin production (rather than pituitary production) might be a useful therapeutic approach.
Stevens
A
A
Endocrine Sciences Research Group, University of Manchester, UK. fras@fsl.ser.man.ac.uk
Ray
D W
DW
Worthington
J
J
Davis
J R
JR
D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000503:physiopathology; D008214:Lymphocytes / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011388:Prolactin / Q000096:biosynthesis* / Q000235:genetics*
D011388:Prolactin