The role of IL‑16 gene polymorphisms in endometriosis

Matalliotakis,Michail; Zervou,Maria  I.; Eliopoulos,Elias; Matalliotaki,Charoula; Rahmioglu,Nilufer; Kalogiannidis,Ioannis; Zondervan,Krina; Spandidos,Demetrios   A.; Matalliotakis,Ioannis; Goulielmos,George  N.

doi:10.3892/ijmm.2018.3368

The role of IL‑16 gene polymorphisms in endometriosis

Authors:
- Michail Matalliotakis
- Maria I. Zervou
- Elias Eliopoulos
- Charoula Matalliotaki
- Nilufer Rahmioglu
- Ioannis Kalogiannidis
- Krina Zondervan
- Demetrios A. Spandidos
- Ioannis Matalliotakis
- George N. Goulielmos
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Venizeleio General Hospital, 71409 Heraklion, Crete, Greece, Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece, Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece, Wellcome Trust Centre for Human Genetics, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, OX3 7BN Oxford, UK, 3rd Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Crete, Greece
Published online on: January 9, 2018 https://doi.org/10.3892/ijmm.2018.3368
Pages: 1469-1476
Copyright: © Matalliotakis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Endometriosis is one of the most common gynecological diseases affecting up to 10% of the female population of childbearing age and a major cause of pain and infertility. It is influenced by multiple genetic, epigenetic and environmental factors. Interleukin‑16 (IL‑16) is a proinflammatory cytokine playing a pivotal role in many inflammatory and autoimmune diseases as well as in the pathogenesis of endometriosis. The aim of the present study was to evaluate the association of two IL‑16 gene single nucleotide polymorphisms (SNPs), rs4072111 and rs11556218, with the risk of endometriosis in women from Greece as well as to gain insight about the structural consequences of these two exonic SNPs regarding development of the disease. A total of 159 women with endometriosis (stages I‑IV) hospitalized for endometriosis, diagnosed by laparoscopic intervention and histologically confirmed, and 146 normal controls were recruited and genotyped. Subjects were genotyped using a polymerase chain reaction restriction fragment length polymorphism (PCR‑RFLP) strategy. A significant association was detected regarding the GG and GT genotype as well as ‘G’ allele of rs11556218 in patients with endometriosis. The rs4072111 SNP of the IL‑16 gene was not found to be associated with an increased susceptibility to endometriosis either for all patients (stages I‑IV) or for stage III and IV of the disease only. Our results demonstrated that rs11556218 is associated with endometriosis in Greek women, probably by resulting in the aberrant expression of IL‑16, as suggested by the bioinformatics analysis conducted on the SNP‑derived protein sequences, which indicated a possible association between mutation and functional modification of Pro‑IL‑16.

View Figures

View References

1	Giudice LC and Kao LC: Endometriosis. Lancet. 364:1789–1799. 2004. View Article : Google Scholar : PubMed/NCBI
2	Halis G and Arici A: Endometriosis and inflammation in infertility. Ann N Y Acad Sci. 1034:300–315. 2004. View Article : Google Scholar
3	Burney RO and Giudice LC: Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 98:511–519. 2012. View Article : Google Scholar : PubMed/NCBI
4	Bazot M, Lafont C, Rouzier R, Roseau G, Thomassin-Naggara I and Daraï E: Diagnostic accuracy of physical examination, trans-vaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis. Fertil Steril. 92:1825–1833. 2009. View Article : Google Scholar
5	Koninckx PR, Ussia A, Adamyan L, Wattiez A and Donnez J: Deep endometriosis: Definition, diagnosis, and treatment. Fertil Steril. 98:564–571. 2012. View Article : Google Scholar : PubMed/NCBI
6	Maroun P, Cooper MJ, Reid GD and Keirse MJ: Relevance of gastrointestinal symptoms in endometriosis. Aust N Z J Obstet Gynaecol. 49:411–414. 2009. View Article : Google Scholar : PubMed/NCBI
7	Varma R, Rollason T, Gupta JK and Maher ER: Endometriosis and the neoplastic process. Reproduction. 127:293–304. 2004. View Article : Google Scholar : PubMed/NCBI
8	Sampson J: Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 14:422–469. 1927. View Article : Google Scholar
9	Batt RE, Smith RA, Buck GM, Severino MF and Naples JD: Müllerianosis. Prog Clin Biol Res. 323:413–426. 1990.
10	Vercellini P, Viganò P, Somigliana E and Fedele L: Endometriosis: Pathogenesis and treatment. Nat Rev Endocrinol. 10:261–275. 2014. View Article : Google Scholar
11	Simpson JL, Elias S, Malinak LR and Buttram VC Jr: Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol. 137:327–331. 1980. View Article : Google Scholar : PubMed/NCBI
12	Lamb K, Hoffmann RG and Nichols TR: Family trait analysis: A case-control study of 43 women with endometriosis and their best friends. Am J Obstet Gynecol. 154:596–601. 1986. View Article : Google Scholar : PubMed/NCBI
13	Coxhead D and Thomas EJ: Familial inheritance of endometriosis in a British population. A case control study. J Obstet Gynaecol. 13:42–44. 1993. View Article : Google Scholar
14	Stefansson H, Geirsson RT, Steinthorsdottir V, Jonsson H, Manolescu A, Kong A, Ingadottir G, Gulcher J and Stefansson K: Genetic factors contribute to the risk of developing endometriosis. Hum Reprod. 17:555–559. 2002. View Article : Google Scholar : PubMed/NCBI
15	Treloar SA, O'Connor DT, O'Connor VM and Martin NG: Genetic influences on endometriosis in an Australian twin sample. simplesueT@qimr.edu.au. Fertil Steril. 71:701–710. 1999. View Article : Google Scholar : PubMed/NCBI
16	Saha R, Pettersson HJ, Svedberg P, Olovsson M, Bergqvist A, Marions L, Tornvall P and Kuja-Halkola R: Heritability of endometriosis. Fertil Steril. 104:947–952. 2015. View Article : Google Scholar : PubMed/NCBI
17	Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ and Zhao K: Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 40:897–903. 2008. View Article : Google Scholar : PubMed/NCBI
18	Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, et al: Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 146:1016–1028. 2011. View Article : Google Scholar : PubMed/NCBI
19	Falconer H, D'Hooghe T and Fried G: Endometriosis and genetic polymorphisms. Obstet Gynecol Surv. 62:616–628. 2007. View Article : Google Scholar : PubMed/NCBI
20	Nyholt DR, Low SK, Anderson CA, Painter JN, Uno S, Morris AP, MacGregor S, Gordon SD, Henders AK, Martin NG, et al: Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat Genet. 44:1355–1359. 2012. View Article : Google Scholar : PubMed/NCBI
21	Albertsen HM, Chettier R, Farrington P and Ward K: Genome-wide association study link novel loci to endometriosis. PLoS One. 8:e582572013. View Article : Google Scholar : PubMed/NCBI
22	Rahmioglu N, Nyholt DR, Morris AP, Missmer SA, Montgomery GW and Zondervan KT: Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets. Hum Reprod Update. 20:702–716. 2014. View Article : Google Scholar : PubMed/NCBI
23	Zondervan KT, Rahmioglu N, Morris AP, Nyholt DR, Montgomery GW, Becker CM and Missmer SA: Beyond endometriosis genome-wide association study: From genomics to phenomics to the patient. Semin Reprod Med. 34:242–254. 2016. View Article : Google Scholar : PubMed/NCBI
24	Uimari O, Rahmioglu N, Nyholt DR, Vincent K, Missmer SA, Becker C, Morris AP, Montgomery GW and Zondervan KT: Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis. Hum Reprod. 32:780–793. 2017. View Article : Google Scholar : PubMed/NCBI
25	Kobayashi H, Imanaka S, Nakamura H and Tsuji A: Understanding the role of epigenomic, genomic and genetic alterations in the development of endometriosis (Review). Mol Med Rep. 9:1483–1505. 2014. View Article : Google Scholar : PubMed/NCBI
26	Rahmioglu N, Montgomery GW and Zondervan KT: Genetics of endometriosis. Wom Health Lond. 11:577–586. 2015. View Article : Google Scholar
27	Sapkota Y, Steinthorsdottir V, Morris AP, Fassbender A, Rahmioglu N, De Vivo I, Buring JE, Zhang F, Edwards TL, Jones S, et al: iPSYCH-SSI-Broad Group: Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nat Commun. 8:155392017. View Article : Google Scholar
28	Sapkota Y, Attia J, Gordon SD, Henders AK, Holliday EG, Rahmioglu N, MacGregor S, Martin NG, McEvoy M, Morris AP, et al: Genetic burden associated with varying degrees of disease severity in endometriosis. Mol Hum Reprod. 21:594–602. 2015. View Article : Google Scholar : PubMed/NCBI
29	Drosdzol-Cop A and Skrzypulec-Plinta V: Selected cytokines and glycodelin A levels in serum and peritoneal fluid in girls with endometriosis. J Obstet Gynaecol Res. 38:1245–1253. 2012. View Article : Google Scholar : PubMed/NCBI
30	Athayde N, Romero R, Maymon E, Gomez R, Pacora P, Araneda H and Yoon BH: A role for the novel cytokine RANTES in pregnancy and parturition. Am J Obstet Gynecol. 181:989–994. 1999. View Article : Google Scholar : PubMed/NCBI
31	Thornton CA, Holloway JA, Shute JK, Holloway JW, Diaper ND and Warner JO: Human mid-gestation amniotic fluid contains interleukin-16 bioactivity. Immunology. 126:543–551. 2009. View Article : Google Scholar : PubMed/NCBI
32	Mathy NL, Scheuer W, Lanzendörfer M, Honold K, Ambrosius D, Norley S and Kurth R: Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunology. 100:63–69. 2000. View Article : Google Scholar : PubMed/NCBI
33	Brait VH, Arumugam TV, Drummond GR and Sobey CG: Importance of T lymphocytes in brain injury, immunodeficiency, and recovery after cerebral ischemia. J Cereb Blood Flow Metab. 32:598–611. 2012. View Article : Google Scholar : PubMed/NCBI
34	Baier M, Bannert N, Werner A, Lang K and Kurth R: Molecular cloning, sequence, expression, and processing of the interleukin 16 precursor. Proc Natl Acad Sci USA. 94:5273–5277. 1997. View Article : Google Scholar : PubMed/NCBI
35	Center DM, Kornfeld H and Cruikshank WW: Interleukin-16. Int J Biochem Cell Biol. 29:1231–1234. 1997. View Article : Google Scholar
36	Chupp GL, Wright EA, Wu D, Vallen-Mashikian M, Cruikshank WW, Center DM, Kornfeld H and Berman JS: Tissue and T cell distribution of precursor and mature IL-16. J Immunol. 161:3114–3119. 1998.PubMed/NCBI
37	Zhang Y, Center DM, Wu DM, Cruikshank WW, Yuan J, Andrews DW and Kornfeld H: Processing and activation of pro-interleukin-16 by caspase-3. J Biol Chem. 273:1144–1149. 1998. View Article : Google Scholar : PubMed/NCBI
38	Bowler RP, Bahr TM, Hughes G, Lutz S, Kim YI, Coldren CD, Reisdorph N and Kechris KJ: Integrative omics approach identifies interleukin-16 as a biomarker of emphysema. OMICS. 17:619–626. 2013. View Article : Google Scholar : PubMed/NCBI
39	Tong Z, Li Q, Zhang J, Wei Y, Miao G and Yang X: Association between interleukin 6 and interleukin 16 gene polymorphisms and coronary heart disease risk in a Chinese population. J Int Med Res. 41:1049–1056. 2013. View Article : Google Scholar : PubMed/NCBI
40	Liu XL, Du JZ, Zhou YM, Shu QF and Li YG: Interleukin-16 polymorphism is associated with an increased risk of ischemic stroke. Mediators Inflamm. 2013:5647502013. View Article : Google Scholar : PubMed/NCBI
41	Khoshbakht T, Soosanabadi M, Neishaboury M, Kamali K, Karimlou M, Bazazzadegan N and Khorram Khorshid HR: An association study on IL16 gene polymorphisms with the risk of sporadic Alzheimer's disease. Avicenna J Med Biotechnol. 7:128–132. 2015.PubMed/NCBI
42	Romani S, Hosseini SM, Mohebbi SR, Kazemian S, Derakhshani S, Khanyaghma M, Azimzadeh P, Sharifian A and Zali MR: Interleukin-16 gene polymorphisms are considerable host genetic factors for patients' susceptibility to chronic hepatitis B infection. Hepat Res Treat. 2014:7907532014.
43	Glas J, Török H-P, Unterhuber H, Radlmayr M and Folwaczny C: The -295T-to-C promoter polymorphism of the IL-16 gene is associated with Crohn's disease. Clin Immunol. 106:197–200. 2003. View Article : Google Scholar : PubMed/NCBI
44	Gu XJ, Cui B, Zhao ZF, Chen HY, Li XY, Wang S, Ning G and Zhao YJ: Association of the interleukin (IL)-16 gene polymorphisms with Graves' disease. Clin Immunol. 127:298–302. 2008. View Article : Google Scholar : PubMed/NCBI
45	Xue H, Gao L, Wu Y, Fang W, Wang L, Li C, Li Y, Liang W and Zhang L: The IL-16 gene polymorphisms and the risk of the systemic lupus erythematosus. Clin Chim Acta. 403:223–225. 2009. View Article : Google Scholar : PubMed/NCBI
46	Luo SX, Li S, Zhang XH, Zhang JJ, Long GH, Dong GF, Su W, Deng Y, Liu Y, Zhao JM and Qin X: Genetic polymorphisms of interleukin-16 and risk of knee osteoarthritis. PLoS One. 10:e01234422015. View Article : Google Scholar : PubMed/NCBI
47	Gao LB, Rao L, Wang YY, Liang WB, Li C, Xue H, Zhou B, Sun H, Li Y, Lv ML, et al: The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer. Carcinogenesis. 30:295–299. 2009. View Article : Google Scholar
48	Li S, Deng Y, Chen ZP, Huang S, Liao XC, Lin LW, Li H, Peng T, Qin X and Zhao JM: Genetic polymorphism of interleukin-16 influences susceptibility to HBV-related hepatocellular carcinoma in a Chinese population. Infect Genet Evol. 11:2083–2088. 2011. View Article : Google Scholar : PubMed/NCBI
49	Batai K, Shah E, Murphy AB, Newsome J, Ruden M, Ahaghotu C and Kittles RA: Fine-mapping of IL16 gene and prostate cancer risk in African Americans. Cancer Epidemiol Biomarkers Prev. 21:2059–2068. 2012. View Article : Google Scholar : PubMed/NCBI
50	Mo CJ, Peng QL, He Y, Wang J, Xie L, Li TJ, Li S and Qin X: Positive association between IL-16 rs11556218 T/G polymorphism and cancer risk: A meta-analysis. Asian Pac J Cancer Prev. 15:4697–4703. 2014. View Article : Google Scholar : PubMed/NCBI
51	Poulat F, de Santa Barbara P, Desclozeaux M, Soullier S, Moniot B, Bonneaud N, Boizet B and Berta P: The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains. J Biol Chem. 272:7167–7172. 1997. View Article : Google Scholar : PubMed/NCBI
52	Fanning AS and Anderson JM: Protein-protein interactions: PDZ domain networks. Curr Biol. 6:1385–1388. 1996. View Article : Google Scholar : PubMed/NCBI
53	Sherman DL and Brophy PJ: A tripartite nuclear localization signal in the PDZ-domain protein L-periaxin. J Biol Chem. 275:4537–4540. 2000. View Article : Google Scholar : PubMed/NCBI
54	Hsueh YP, Wang TF, Yang FC and Sheng M: Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature. 404:298–302. 2000. View Article : Google Scholar : PubMed/NCBI
55	Azimzadeh P, Khorram Khorshid HR, Akhondi MM and Shirazi A: Association of interleukin-16 polymorphisms with disease progression and susceptibility in endometriosis. Int J Immunogenet. 43:297–302. 2016. View Article : Google Scholar : PubMed/NCBI
56	Hsieh YY, Bau DT, Chang CC, Tsai CH, Chen CP and Tsai FJ: XRCC4 codon 247A and XRCC4 promoter -1394T related genotypes but not XRCC4 intron 3 gene polymorphism are associated with higher susceptibility for endometriosis. Mol Reprod Dev. 75:946–951. 2008. View Article : Google Scholar : PubMed/NCBI
57	Altinkaya SO, Ugur M, Ceylaner G, Ozat M, Gungor T and Ceylaner S: Vascular endothelial growth factor +405 C/G poly morphism is highly associated with an increased risk of endometriosis in Turkish women. Arch Gynecol Obstet. 283:267–272. 2011. View Article : Google Scholar
58	Matalliotakis M, Zervou MI, Matalliotaki C, Rahmioglu N, Koumantakis G, Kalogiannidis I, Prapas I, Zondervan K, Spandidos DA, Matalliotakis I and Goulielmos GN: The role of gene polymorphisms in endometriosis. Mol Med Rep. 16:5881–5886. 2017. View Article : Google Scholar : PubMed/NCBI
59	The American Fertility Society: Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril. 43:351–352. 1985. View Article : Google Scholar : PubMed/NCBI
60	Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Gallo Cassarino T, Bertoni M, Bordoli L and Schwede T: SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 42:W252–258. 2014. View Article : Google Scholar : PubMed/NCBI
61	Sato M, Koshiba S, Inoue M, Kigawa T and Yokoyama S: RIKEN Structural Genomics/Proteomics Initiative, deposition. 2005 05 23;
62	Kim HS: Assignment of human interleukin 16 (IL16) to chromosome 15q26.3 by radiation hybrid mapping. Cytogenet Cell Genet. 84:931999. View Article : Google Scholar : PubMed/NCBI
63	Mori M, Yamada R, Kobayashi K, Kawaida R and Yamamoto K: Ethnic differences in allele frequency of autoimmune-disease- associated SNPs. J Hum Genet. 50:264–266. 2005. View Article : Google Scholar
64	Gregersen PK and Olsson LM: Recent advances in the genetics of autoimmune disease. Annu Rev Immunol. 27:363–391. 2009. View Article : Google Scholar : PubMed/NCBI
65	Azimzadeh P, Romani S, Mohebbi SR, Kazemian S, Vahedi M, Almasi S, Fatemi SR and Zali MR: Interleukin-16 (IL-16) gene polymorphisms in Iranian patients with colorectal cancer. J Gastrointestin Liver Dis. 20:371–376. 2011.PubMed/NCBI
66	Gan XL, Lin YH, Zhang Y, Yu TH and Hu LN: Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. DNA Cell Biol. 29:663–667. 2010. View Article : Google Scholar : PubMed/NCBI
67	Kim JG, Kim H, Ku S-y, Kim SH, Choi YM and Kim JH: The association between single nucleotide polymorphisms of interleukin (IL)-10, IL-10 receptor antagtonist and IL-16 genes and endometriosis. Fertil Steril. 100(Suppl): S3642013. View Article : Google Scholar
68	Koga K, Osuga Y, Yoshino O, Hirota Y, Yano T, Tsutsumi O and Taketani Y: Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis. Fertil Steril. 83:878–882. 2005. View Article : Google Scholar : PubMed/NCBI
69	Cheong YC, Shelton JB, Laird SM, Richmond M, Kudesia G, Li TC and Ledger WL: IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions. Hum Reprod. 17:69–75. 2002. View Article : Google Scholar : PubMed/NCBI
70	Somigliana E, Viganò P, Tirelli AS, Felicetta I, Torresani E, Vignali M and Di Blasio AM: Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions. Hum Reprod. 19:1871–1876. 2004. View Article : Google Scholar : PubMed/NCBI
71	Zhang X, Lin J, Deng L, Chen Z and Chen L: Peritoneal fluid and serum concentration of interleukin-16 in women with endometriosis. Acta Obstet Gynecol Scand. 84:297–298. 2005. View Article : Google Scholar : PubMed/NCBI
72	Xiao H, Yang L, Liu J, Jiao Y, Lu L and Zhao H: Protein-protein interaction analysis to identify biomarker networks for endometriosis. Exp Ther Med. 14:4647–4654. 2017.PubMed/NCBI
73	Schadt EE: Molecular networks as sensors and drivers of common human diseases. Nature. 461:218–223. 2009. View Article : Google Scholar : PubMed/NCBI
74	Ma Y, Tian J, Cen H, Li J, Xu WD, Wang DG, Pan HF and Ye DQ: Association of c-Jun gene polymorphism with susceptibility to systemic lupus erythematosus in a Chinese population. DNA Cell Biol. 31:1274–1278. 2012. View Article : Google Scholar : PubMed/NCBI
75	Bannert N, Vollhardt K, Asomuddinov B, Haag M, König H, Norley S and Kurth R: PDZ Domain-mediated interaction of interleukin-16 precursor proteins with myosin phosphatase targeting subunits. J Biol Chem. 278:42190–42199. 2003. View Article : Google Scholar : PubMed/NCBI
76	Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN and Bourne PE: The Protein Data Bank. Nucleic Acids Res. 28:235–242. 2000. View Article : Google Scholar