Association of the intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms with endometriosis: a systematic review and meta-analysis

Background Reported associations of the G241R and K469E polymorphisms of the intercellular adhesion molecule-1 gene (ICAM-1) gene with endometriosis have differed in magnitude.

In a meta-analysis of six published case–control studies (from five articles), we estimated risk [odds ratio (OR) 95 % confidence intervals (CI)] of associations with these polymorphisms using the Review Manager 5.3 software.

Based on 1213 cases and 1103 controls, overall analysis showed significant increased risk in the homozygous (OR 2.83, 95 % CI 0.99–8.10, p = 0.05), dominant (OR 1.86, 95 % CI 1.00–3.46, p = 0.05) and codominant (OR 2.15, 95 % CI 1.06–4.35, p = 0.03) models. Confined to the studies in Hardy–Weinberg Equilibrium erased the significance (OR 1.59–2.59, 95 % CI 0.81–8.22, p = 0.10–0.15). Asian effects were variable (OR 0.93–1.09, p = 0.50–0.57), but Caucasian effects were not (OR 4.09–13.60, p < 0.0001). Independent data for the late stages of endometriosis suggest protection of the ICAM-1 K469E polymorphism among the Asians (OR 0.91–0.95, p = 0.35–0.71). These effects were weak but non-heterogeneous (P heterogeneity = 0.17–0.57, I 2 = 0–40 %).

In summary, strengths of the overall effects were consistency, significance and robustness but limited by their high heterogeneity. These strengths and limitations were also observed in the Caucasian subgroup which when tested for interaction against the contrasting Asian effects, highlighted Caucasian susceptibility (p = 0.004–0.01). The findings are an interplay of strengths and limitations, which warrant awareness of their interpretation as susceptibility markers for this disorder. Similar content being viewed by others

Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799 Ranney B (1980) Endometriosis: pathogenesis, symptoms, and findings. Clin Obstet Gynecol 23:865–874 Missmer SA, Cramer DW (2003) The epidemiology of endometriosis. Obstet Gynecol Clin North Am 30(1):1–19, vii Bianco B, Andre GM, Vilarino FL, Peluso C, Mafra FA, Christofolini DM, Barbosa CP (2012) The possible role of genetic variants in autoimmune-related genes in the development of endometriosis. Hum Immunol 73:306–315 Vigano P, Lattuada D, Somigliana E, Abbiati A, Candiani M, Di Blasio AM (2005) Variants of the CTLA4 gene that segregate with autoimmune diseases are not associated with endometriosis. Mol Hum Reprod 11:745–749 Hsieh YY, Chang CC, Tsai FJ, Peng CT, Yeh LS, Lin CC (2005) Polymorphism for transforming growth factor beta 1–509 (TGF-B1-509): association with endometriosis. Biochem Genet 43:203–210 Teramoto M, Kitawaki J, Koshiba H, Kitaoka Y, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Matsushita M, Maruya E, Saji H, Ohta M, Honjo H (2004) Genetic contribution of tumor necrosis factor (TNF)-alpha gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility. Am J Reprod Immunol 51:352–357 Vigano P, Infantino M, Lattuada D, Lauletta R, Ponti E, Somigliana E, Vignali M, DiBlasio AM (2003) Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in endometriosis. Mol Hum Reprod 9:47–52 Hopkins AM, Baird AW, Nusrat A (2004) ICAM-1: targeted docking for exogenous as well as endogenous ligands. Adv Drug Deliv Rev 56:763–778 van de Stolpe A, van der Saag PT (1996) Intercellular adhesion molecule-1. J Mol Med (Berlin, Germany) 74:13–33 Vigano P, Somigliana E, Gaffuri B, Santorsola R, Busacca M, Vignali M (2000) Endometrial release of soluble intercellular adhesion molecule 1 and endometriosis: relationship to the extent of the disease. Obst Gynecol 95:115–118 Vigano P, Pardi R, Magri B, Busacca M, Di Blasio AM, Vignali M (1994) Expression of intercellular adhesion molecule-1 (ICAM-1) on cultured human endometrial stromal cells and its role in the interaction with natural killers. Am J Reprod Immunol 32:139–145 Robledo O, Papaioannou A, Ochietti B, Beauchemin C, Legault D, Cantin A, King PD, Daniel C, Alakhov VY, Potworowski EF, St-Pierre Y (2003) ICAM-1 isoforms: specific activity and sensitivity to cleavage by leukocyte elastase and cathepsin g. Eur J Immunol 33:1351–1360 Cotran RS, Mayadas-Norton T (1998) Endothelial adhesion molecules in health and disease. Pathol-Biol 46:164–170 Vora DK, Rosenbloom CL, Beaudet AL, Cottingham RW (1994) Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster. Genomics 21:473–477 Wells OC, Peterson, Welch et al (2011) The Newcastle–ottawa scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. Ottawa Health Research Institute. www.ohrica/programs/clinical_epidemiology/oxfordasp. Accessed 01 Oct 2014 Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748 DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188 Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826 Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clinical research ed) 327:557–560 Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558 Ioannidis JP, Trikalinos TA (2007) The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. CMAJ 176:1091–1096 Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. PLoS Med 6:e1000097 Aghajanpour L, Mashayekhi F, Rajaei F (2010) Intercellular adhesion molecule-1 (ICAM-1) gene polymorphism and endometriosis in northern iran. Arch Gynecol Obst 283:1035–1039 Chae SJ, Lee GH, Choi YM, Hong MA, Kim JM, Lee KS, Ku SY, Moon SY (2010) Intercellular adhesion molecule-1 and interleukin-6 gene polymorphisms in patients with advanced-stage endometriosis. Gynecol Obst Invest 70:34–39 Kitawaki J, Kiyomizu M, Obayashi H, Ohta M, Ishihara H, Hasegawa G, Nakamura N, Yoshikawa T, Honjo H (2006) Synergistic effect of interleukin-6 promoter (IL6-634C/G) and intercellular adhesion molecule-1 (ICAM-1469K/E) gene polymorphisms on the risk of endometriosis in Japanese women. Am J Reprod Immunol 56:267–274 Yamashita M, Yoshida S, Kennedy S, Ohara N, Motoyama S, Maruo T (2005) Association study of endometriosis and intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in a Japanese population. J Soc Gynecol Investig 12:267–271 Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314 Hubbard AK, Rothlein R (2000) Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic Biol Med 28:1379–1386 Porter JC, Bracke M, Smith A, Davies D, Hogg N (2002) Signaling through integrin LFA-1 leads to filamentous actin polymerization and remodeling, resulting in enhanced t cell adhesion. J Immunol 168:6330–6335 Vicente-Manzanares M, Sanchez-Madrid F (2004) Role of the cytoskeleton during leukocyte responses. Nat Rev 4:110–122 Somigliana E, Vigano P, Gaffuri B, Guarneri D, Busacca M, Vignali M (1996) Human endometrial stromal cells as a source of soluble intercellular adhesion molecule (ICAM)-1 molecules. Hum Reprod (Oxford, England) 11:1190–1194 Wu MH, Yang BC, Hsu CC, Lee YC, Huang KE (1998) The expression of soluble intercellular adhesion molecule-1 in endometriosis. Fertil Steril 70:1139–1142 De Placido G, Alviggi C, Di Palma G, Carravetta C, Matarese G, Landino G, Racioppi L (1998) Serum concentrations of soluble human leukocyte class i antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions. Hum Reprod (Oxford, England) 13:3206–3210 Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA (1988) Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52:925–933 Diamond MS, Staunton DE, Marlin SD, Springer TA (1991) Binding of the integrin mac-1 (CD11B/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell 65:961–971 Macchioni P, Boiardi L, Casali B, Nicoli D, Farnetti E, Salvarani C (2000) Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis. Clin Exp Rheumatol 18:553–558 Boiardi L, Salvarani C, Casali B, Olivieri I, Ciancio G, Cantini F, Salvi F, Malatesta R, Govoni M, Trotta F, Filippini D, Paolazzi G, Nicoli D, Farnetti E, Macchioni L (2001) Intercellular adhesion molecule-1 gene polymorphisms in Behcet’s disease. J Rheumatol 28:1283–1287 Salvarani C, Casali B, Boiardi L, Ranzi A, Macchioni P, Nicoli D, Farnetti E, Brini M, Portioli I (2000) Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity. J Rheumatol 27:1215–1221 Gadek TR, Burdick DJ, McDowell RS, Stanley MS, Marsters JC, Jr., Paris KJ, Oare DA, Reynolds ME, Ladner C, Zioncheck KA, Lee WP, Gribling P, Dennis MS, Skelton NJ, Tumas DB, Clark KR, Keating SM, Beresini MH, Tilley JW, Presta LG, Bodary SC (2002) Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule. Science (New York, NY) 295:1086–1089 Mao D, Lu S, Li N, Zhang Y, Long M (2011) Conformational stability analyses of alpha subunit i domain of LFA-1 and MAC-1. PLoS One 6(8):e24188 Iwao M, Morisaki H, Morisaki T (2004) Single-nucleotide polymorphism g.1548G > A (E469K) in human ICAM-1 gene affects mrna splicing pattern and TPA-induced apoptosis. Biochem Biophys Res Commun 317:729–735 Brown A, Turner L, Christoffersen S, Andrews KA, Szestak T, Zhao Y, Larsen S, Craig AG, Higgins MK (2013) Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1. J Biol Chem 288:5992–6003 Pare G, Ridker PM, Rose L, Barbalic M, Dupuis J, Dehghan A, Bis JC, Benjamin EJ, Shiffman D, Parker AN, Chasman DI (2011) Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci. PLoS Genet 7:e1001374 Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24:1291–1306 Conflict of interest The authors have no conflicts of interest to declare. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Pabalan, N., Jarjanazi, H., Christofolini, D.M. et al. Association of the intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms with endometriosis: a systematic review and meta-analysis. Arch Gynecol Obstet 292, 843–851 (2015). https://doi.org/10.1007/s00404-015-3705-2 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-015-3705-2