Analysis of vitamin D-binding protein (VDBP) gene polymorphisms in Korean women with and without endometriosis

Min-Chul Cho, Jin Hyun Kim, Myeong Hee Jung, In Ae Cho, Hyen Chul Jo, Jeong Kyu Shin, Soon Ae Lee, Won Jun Choi, Jong Hak Lee, Min-Chul Cho, Jin Hyun Kim, Myeong Hee Jung, In Ae Cho, Hyen Chul Jo, Jeong Kyu Shin, Soon Ae Lee, Won Jun Choi, Jong Hak Lee

Abstract

Objective: Vitamin D-binding protein (VDBP) mediates various biological processes in humans. The goal of this study was to investigate whether VDBP gene polymorphisms could predispose Korean women to endometriosis.

Methods: We prospectively enrolled women with endometriosis (n = 16) and healthy controls (n = 16). Total serum 25-hydroxyl vitamin D (25(OH)D) concentrations were measured using an Elecsys vitamin D total kit. Levels of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using a vitamin D BP Quantikine ELISA kit. DNA was extracted using a DNeasy blood & tissue kit. Two singlenucleotide polymorphisms (SNPs; rs4588 and rs7041) in GC, the gene that codes for VDBP, were analyzed using a TaqMan SNP genotyping assay kit. The functional variant of VDBP was determined based on the results of the two SNPs.

Results: Gravidity and parity were significantly lower in the endometriosis patients than in the control group, but serum CA-125 levels and the erythrocyte sedimentation rate were significantly higher. Total serum 25(OH)D levels in the endometriosis patients were significantly lower than in the control group. However, serum bioavailable 25(OH)D, free 25(OH)D, and VDBP levels did not differ significantly between the endometriosis and control groups. The genotypes and allele frequencies of GC were similar in both groups.

Conclusion: Korean women with endometriosis had lower total serum 25(OH)D concentrations than controls. Neither serum VDBP concentrations nor polymorphisms in the gene coding for VDBP were associated with endometriosis. Further studies are needed to investigate the pathophysiology and clinical implications of 25(OH)D and VDBP in endometriosis.

Keywords: Endometriosis; Genetic polymorphism; Vitamin D; Vitamin D-binding protein.

Conflict of interest statement

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Figures

Figure 1.
Figure 1.
Comparison of serum total, bioavailable, and free 25-hydroxyl vitamin D (25(OH)D) concentrations between subjects with endometriosis and healthy controls. (A) Total 25(OH)D, a)p= 0.017. (B) Bioavailable 25(OH)D, p= 0.858. (C) Free 25(OH)D, p= 0.961. The independent sample t-test was used for the statistical analysis.
Figure 2.
Figure 2.
Comparison of serum vitamin D-binding protein (VDBP) concentrations in women with endometriosis and healthy controls (p= 0.323). The independent-sample t-test was used for the statistical analysis.

References

    1. D’Hooghe TM. Endometriosis. In: Berek JS, editor. Berek & Novak’s gynecology. Philadelphia: Lippincott Williams & Wilkins; 2012. pp. 505–6.
    1. van der Linden PJ. Theories on the pathogenesis of endometriosis. Hum Reprod. 1996;11 Suppl 3:53–65.
    1. D’Hooghe TM, Hill JA. Immunobiology of endometriosis. In: Bronson RA, Alexander NJ, Anderson DJ, Branch DW, Kutteh WH, editors. Immunology of reproduction. Cambridge: Blackwell; 1996. pp. 322–58.
    1. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17:2715–24.
    1. Kyama CM, Mihalyi A, Simsa P, Falconer H, Fulop V, Mwenda JM, et al. Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis. Front Biosci (Elite Ed) 2009;1:444–54.
    1. Akoum A, Kong J, Metz C, Beaumont MC. Spontaneous and stimulated secretion of monocyte chemotactic protein-1 and macrophage migration inhibitory factor by peritoneal macrophages in women with and without endometriosis. Fertil Steril. 2002;77:989–94.
    1. Christodoulakos G, Augoulea A, Lambrinoudaki I, Sioulas V, Creatsas G. Pathogenesis of endometriosis: the role of defective ‘immunosurveillance’. Eur J Contracept Reprod Health Care. 2007;12:194–202.
    1. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80(6 Suppl):1689S–1696S.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.
    1. Bhan I, Powe CE, Berg AH, Ankers E, Wenger JB, Karumanchi SA, et al. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int. 2012;82:84–9.
    1. Lemire JM, Archer DC. 1,25-Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest. 1991;87:1103–7.
    1. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr. 1998;128:68–72.
    1. Mikkelsen M, Jacobsen P, Henningsen K. Possible localization of Gc-System on chromosome 4: loss of long arm 4 material associated with father-child incompatibility within the Gc-System. Hum Hered. 1977;27:105–7.
    1. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008;88:491S–499S.
    1. Meier U, Gressner O, Lammert F, Gressner AM. Gc-globulin: roles in response to injury. Clin Chem. 2006;52:1247–53.
    1. Yamamoto N, Naraparaju VR. Vitamin D3-binding protein as a precursor for macrophage activating factor in the inflammationprimed macrophage activation cascade in rats. Cell Immunol. 1996;170:161–7.
    1. Kanda S, Mochizuki Y, Miyata Y, Kanetake H, Yamamoto N. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis. J Natl Cancer Inst. 2002;94:1311–9.
    1. Yamamoto N, Kumashiro R. Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells. J Immunol. 1993;151:2794–802.
    1. Zhou L, Zhang X, Chen X, Liu L, Lu C, Tang X, et al. GC Glu416Asp and Thr420Lys polymorphisms contribute to gastrointestinal cancer susceptibility in a Chinese population. Int J Clin Exp Med. 2012;5:72–9.
    1. Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, et al. The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev. 2008;17:1339–43.
    1. Larcombe L, Mookherjee N, Slater J, Slivinski C, Singer M, Whaley C, et al. Vitamin D in a northern Canadian first nation population: dietary intake, serum concentrations and functional gene polymorphisms. PLoS One. 2012;7:e49872.
    1. Szczepanska M, Mostowska A, Wirstlein P, Skrzypczak J, Misztal M, Jagodzinski PP. Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility. Mol Med Rep. 2015;12:7109–15.
    1. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80(6 Suppl):1678S–1688S.
    1. Faserl K, Golderer G, Kremser L, Lindner H, Sarg B, Wildt L, et al. Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2011;96:E233–41.
    1. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63:954–9.
    1. Heijboer AC, Blankenstein MA, Kema IP, Buijs MM. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem. 2012;58:543–8.
    1. Arnaud J, Constans J. Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP) Hum Genet. 1993;92:183–8.
    1. Song M, Konijeti GG, Yuan C, Ananthakrishnan AN, Ogino S, Fuchs CS, et al. Plasma 25-hydroxyvitamin d, vitamin D binding protein, and risk of colorectal cancer in the nurses’ health study. Cancer Prev Res (Phila) 2016;9:664–72.
    1. Shen A, Xu S, Ma Y, Guo H, Li C, Yang C, et al. Diagnostic value of serum CA125, CA19-9 and CA15-3 in endometriosis: a metaanalysis. J Int Med Res. 2015;43:599–609.
    1. Vodolazkaia A, Bossuyt X, Fassbender A, Kyama CM, Meuleman C, Peeraer K, et al. A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis. Reprod Biol Endocrinol. 2011;9:113.
    1. Lermann J, Mueller A, Korber F, Oppelt P, Beckmann MW, Dittrich R, et al. Evaluation of high-sensitivity C-reactive protein in comparison with C-reactive protein as biochemical serum markers in women with endometriosis. Fertil Steril. 2010;93:2125–9.
    1. Kianpour M, Nematbakhsh M, Ahmadi SM. C-reactive protein of serum and peritoneal fluid in endometriosis. Iran J Nurs Midwifery Res. 2012;17(2 Suppl 1):S115–9.
    1. Osei-Bimpong A, Meek JH, Lewis SM. ESR or CRP? A comparison of their clinical utility. Hematology. 2007;12:353–7.
    1. Lee DH, Park KS, Cho MC. Laboratory confirmation of the effect of occupational sun exposure on serum 25-hydroxyvitamin D concentration. Medicine (Baltimore) 2018;97:e11419.
    1. Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, et al. Effects of 1,25-dihydroxy vitamin D3 on endometriosis. J Clin Endocrinol Metab. 2016;101:2371–9.
    1. Abbas MA, Taha MO, Disi AM, Shomaf M. Regression of endometrial implants treated with vitamin D3 in a rat model of endometriosis. Eur J Pharmacol. 2013;715:72–5.
    1. Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod. 2012;27:3321–7.
    1. Borkowski J, Gmyrek GB, Madej JP, Nowacki W, Goluda M, Gabrys M, et al. Serum and peritoneal evaluation of vitamin D-binding protein in women with endometriosis. Postepy Hig Med Dosw (Online) 2008;62:103–9.
    1. Ferrero S, Gillott DJ, Anserini P, Remorgida V, Price KM, Ragni N, et al. Vitamin D binding protein in endometriosis. J Soc Gynecol Investig. 2005;12:272–7.
    1. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013;369:1991–2000.
    1. Yao S, Hong CC, Bandera EV, Zhu Q, Liu S, Cheng TD, et al. Demographic, lifestyle, and genetic determinants of circulating concentrations of 25-hydroxyvitamin D and vitamin D-binding protein in African American and European American women. Am J Clin Nutr. 2017;105:1362–71.
    1. Knudsen CS, Nexo E, Hojskov CS, Heickendorff L. Analytical validation of the Roche 25-OH Vitamin D Total assay. Clin Chem Lab Med. 2012;50:1965–8.

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