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J Clin Endocrinol Metab. 2011 Jan;96(1):E233-41. doi: 10.1210/jc.2010-1532. Epub 2010 Oct 27.

Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis.

Author information

1
Department of Gynecologic Endocrinology and Reproductive Medicine, Innsbruck Medical University, Innsbruck, Austria.

Abstract

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-scale liquid chromatography-electrospray ionization-mass spectrometry 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.

PMID:
20980430
DOI:
10.1210/jc.2010-1532
[Indexed for MEDLINE]

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