Polymorphism in Vitamin D-Binding Protein as a Genetic Risk Factor in the Pathogenesis of Endometriosis

• DOI: 10.1210/jc.2010-1532
• Publication Date: 2010-10-28T02:18:36Z
• Authors: Klaus Faserl; Georg Golderer; Leopold Kremser; Herbert Lindner; Bettina Sarg; Ludwig Wildt; Beata Seeber
• Keywords: Polymorphism, Genetic; Vitamin D-Binding Protein; Endometriosis; Mass Spectrometry; 3. Good health; 03 medical and health sciences; Cross-Sectional Studies; 0302 clinical medicine; Risk Factors; Humans; Electrophoresis, Gel, Two-Dimensional; Female; Alleles; Chromatography, Liquid

Context: Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. Objective: Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. Design and Setting: This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. Patients: Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. Intervention: Blood was collected preoperatively. Main Outcome Measure: Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. Results: We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P < 0.02). Analysis of specific allele products using nano-LC-ESI-MS indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. Conclusions: We speculate that the inability to sufficiently activate macrophages’ phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.