- Research
- Open Access
- Published:
Serum concentrations of IL-16 and its genetic polymorphism rs4778889 affect the susceptibility and severity of endometriosis in Nigerian women
BMC Women's Health volume 23, Article number: 253 (2023)
Abstract
Background
Endometriosis is the presence of active ectopic endometrial glands and stroma at other sites outside the uterine cavity. It is a common cause of chronic pelvic pain which is sometimes debilitating, and inflammation is one of the known triggers of endometriosis. Interleukins 6 and 16 (IL-6 and IL-16) are proinflammatory cytokines which play essential roles in inflammatory diseases. We therefore investigated the relationship between genetic polymorphisms of interleukins 6 and 16, and the development of endometriosis in Nigerian women.
Method
One hundred and thirty (130) consenting women were consecutively enrolled, sixty-five (65) of whom had endometriosis and 65 age-matched women as reference group, surgically confirmed as not having endometriosis. Spectrophotometric determination of serum concentrations of Interleukins 6 and 16 was carried out and the genotyping of IL-6 (rs1800795) and IL-16 (rs4778889, rs11556218, rs4072111) genes were performed using TaqMan assays.
Results
Serum IL-16 concentration was significantly higher in women with severe chronic pelvic pain compared to those with mild pain (p = 0.023). The C allele of rs4778889 was associated with endometriosis (OR: 1.80, 95% CI: 1.08 – 3.02, p = 0.024).
Conclusion
Serum IL-16 and IL-16 rs4778889 may be important markers for endometriosis in Nigerian, and by extension, African women. Multicentre African studies would clarify this.
What is already known?
• Interleukins play a vital role in the pain pathway.
• A change in serum interleukin concentration has been found in some studies to be associated with some clinical conditions whose manifestations include pain such as osteoarthritis, myocardial infarction, and Crohn's disease.
• Pain is a common manifestation of endometriosis.
• Endometriosis has been associated with polymorphisms in interleukin genes but with conflicting reports.
What are the new findings from this study?
• The minor allele ‘C’ of IL-16 (rs4778889) is associated with endometriosis in Nigerian women with endometriosis.
• There is an association between serum concentration of IL-16 and pain severity in women with endometriosis.
Introduction
Endometriosis is characterised by the presence of active ectopic endometrial glands and stroma at other sites outside the uterine cavity. It is a common condition and up to 71% of affected women usually report pain-related symptoms such as chronic pelvic pain and dysmenorrhoea [1]. It may predispose to infertility in 30 – 50% of women [2]. Diagnosis often presents a challenge, and many cases are diagnosed late [3]. Despite the numerous studies conducted on various aspects, the features of endometriosis remain challenging to manage [4, 5].
The role of interleukins as proinflammatory markers, autoimmune and immune modulators have led to exploration of their effect in the development of endometriosis. Several proinflammatory cytokines, namely interleukins 1, 6, 10 and 16, tumour necrosis factor-α and prostaglandin E have been postulated to play a role in the development of endometriosis [6,7,8].
IL-6 is a multifunctional cytokine with both pro- and anti-inflammatory properties. It is produced by different types of cells, including activated macrophages, monocytes, fibroblasts, activated T lymphocytes and B lymphocytes, and endothelial cells. IL-6 is involved in the control of homeostasis of cell processes, including lipid metabolism, mitochondrial activities, neuroendocrine system function and neuropsychological behaviour [9]. Comparatively, IL-6 presents low levels under normal conditions but is elevated when an event stimulates immune response. Some studies have suggested that IL-6 is a good marker for disease progression in endometriosis [10, 11].
The IL-6 gene is located on chromosome 7p21-24 and is composed of six exons and five introns. rs1800795 (-174G > C) is a common functional SNP in the promoter gene of IL-6, known to affect transcriptional activity and IL-6 concentrations [12, 13].
Interleukin-16 (IL-16), also known as a lymphocyte chemoattractant factor, is a multifunctional proinflammatory cytokine that performs an essential role in many immune and inflammatory responses. IL-16, through the peripheral blood mononuclear cells, stimulates the production of proinflammatory cytokines such as IL-6, IL-1β and TNF-α, which have been demonstrated to play a critical role in the pathogenesis of endometriosis [14]. Koga et al. have shown increased concentrations of IL-16 in the peritoneal fluid of patients with endometriosis and revealed that it may play a role in initiating or sustaining inflammatory responses in the peritoneal cavity.
The gene-encoding IL-16 is mapped to chromosome 15q26.3 in the human genome consisting of seven exons and six introns. IL-16 exists as a 631-amino acid precursor protein, Pro-IL-16, which is cleaved by caspase-3 to release the functionally active C-terminal domain, comprising 121 amino acids [15, 16]. Three common single nucleotide polymorphisms in IL-16 (rs4778889 T/C, rs11556218 T/G, and rs4072111) have been found to be associated with inflammatory diseases like asthma, Crohn's disease, cancer, and ischaemic stroke [17,18,19,20]. In a study conducted among Chinese women, the genotype and allele frequencies of rs4778889 T/C polymorphism were associated with endometriosis and pain phenotype [21].
Many studies have been conducted on interleukin 6 and 16 gene polymorphisms in women with endometriosis but considering the rarity of genetic research into benign gynaecological conditions in Africa, this study which to the best of our knowledge will be the first to be done in Africa, became a necessity.
This study aims to determine serum concentrations of IL-6 and IL-16 in women with endometriosis and investigate whether the genetic polymorphisms of Interleukin 6 (rs1800795G/C) and 16 (rs4072111C/T, rs11556218T/G, rs4778889T/C) are associated with endometriosis and endometriosis-related symptoms in Nigerian women.
Patients and methods
This was a case–control study conducted between October 2019 and June 2021 at the Department of Obstetrics and Gynaecology of the College of Medicine of University of Lagos/ Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos, Nigeria.
All consenting women diagnosed as having endometriosis by laparoscopy, laparotomy, histology or who had shown clinical evidence of response to treatment for endometriosis were recruited as cases. Age-matched women who have had laparoscopy or laparotomy for other benign gynaecological conditions with no evidence of endometriosis at surgery, were recruited as reference group. Women in whom diagnosis was in doubt, or had adenomyosis, cancers, chronic medical illness such as renal disease, cardiovascular disease, diabetes mellitus or chronic infections were excluded from the study.
Participant's information was collected by direct questioning or from case notes using the proforma designed for this study. The information obtained included number of births, symptomatology, and family history of endometriosis or other genetic disorders. A numerical rating scale was used for pain assessment in those who reported chronic pelvic pain as a symptom. Pain score was classified as 0–5 mild, 6–7 moderate, and 8–10 severe [22]. For this study, we defined ascites as fluid accumulation within the peritoneal cavity clinically demonstrable by shifting dullness on percussion of the abdomen or peritoneal fluid accumulations of 500mls or more drained during abdominal paracentesis or other surgical procedures [23, 24]. Four millilitres of peripheral blood was collected from each participant by venepuncture. The collected blood samples were stored at -80 0C until analysis. Spectrophotometric determination of serum Interleukins 6 and 16 concentrations was done using Ray Biotech ELISA kits (RayBiotech Life, Inc., GA, USA).
Genomic DNA was isolated from peripheral blood samples using a spin column DNA extraction kit (Jena Bioscience, Germany) according to the manufacturer's instructions. The DNA concentration was determined using a Nanodrop spectrophotometer One (Thermo Scientific, USA). At the genotyping facility, DNA concentration was determined using Qubit dsDNA reagent and Qubit 4 spectrophotometer. Where necessary, 10 ng/µL of each sample was prepared by dilution as genotyping performs better with similar amounts of sample DNA.
Genotyping of four single nucleotide polymorphisms was performed using TaqMan assays on a QuantStudio 5 real-time PCR system (Thermo Fisher Scientific, Singapore). Primers and master mixes for the TaqMan® SNP genotyping of IL-16 gene (rs4072111 C/T, rs11556218 T/G, and rs4778889 C/T) and IL-6 gene (rs1800795C/G) were obtained from Thermo Fisher Scientific (Table 1).
Briefly, the TaqMan genotyping assays come as 40X, and a working 20X is prepared, and analysis is performed according to the manufacturer’s instructions. The TaqPath ProAmp master mixes, with ROX to equilibrate background, were used to perform the replicate real-time PCR analysis. Twenty-five microlitre (25 µL) reactions were set-up on the standard 96-well QuantStudio 5, containing TaqPath ProAmp master mix (12.5 µL), working 20X TaqMan assay (1.25 µL), sample DNA (10 ng) and PCR-grade water. Each run had two–three no-template controls. The genotyping PCR template was used, with two holds for pre-read (60ºC for 30 s) and denaturation/enzyme activation (95ºC for 5 min), 40 cycles of denature (95ºC for 15 s), anneal/extend (60ºC for 60 s), and finally a post-read hold (60ºC for 30 s). Data collection was done at pre-read, end of each cycle and at post-read. Genotypes were analysed and read off the allelic discrimination plot.
Sample size
A sample size of 128 participants (64 per group) was estimated to give this study a statistical power of 80% at a significance level of 5%, considering 20% attrition for missing data and other contingencies, using sample size calculator for genetic association case–control study accessed via http://osse.bii.a-star.edu.sg/calculation1.php as described in Mondry et al., 2006 [25].
Statistical analysis
Results are presented as frequencies, percentages, and mean ± standard deviation. Test of normality was performed using Shapiro–Wilk test. Serum IL-6 and IL-16 concentrations deviated from the normal distribution and are presented as median [interquartile range]. Differences between continuous variables summarised as means were compared using an independent student's t-test, while serum IL-6 and IL-16 concentrations were compared using the Mann–Whitney U test or Kruskal–Wallis test where appropriate. Frequencies of the patients with endometriosis and the reference group were compared by chi-square test (χ2) or linear-by-linear association. Odds ratios (OR) and 95% confidence intervals (95%CI) were also calculated. All statistical analyses were conducted using SPSS version 27 for Windows and R software with p-value < 0.05 considered significant.
Results
The mean age and body mass index of healthy women (32.8 ± 6.67 years old, 25.3 ± 4.38 kg/m2) compared to those with endometriosis (33.06 ± 6.78 years old, 24.4 ± 4.19 kg/m2) were not significant. Women with endometriosis had a significantly higher frequency of chronic pelvic pain, painful menstruation, painful intercourse, painful defaecation, and painful urination (p < 0.0001), compared to healthy women. Only one woman (1.5%) in the reference group had ascites compared to 22 (33.8%) in the case group. Pleural effusion (16.9%) was only observed in the case group. Thirty-five (53.8%) women with endometriosis had pelvic endometriosis while 29 (44.6%) and 1 (1.5%) had extra-pelvic and both pelvic/extra-pelvic endometriosis, respectively. Majority (93.8%) of women with endometriosis had no family history of endometriosis while 3 (4.6%) reported family history of endometriosis. Endometriosis was diagnosed by laparotomy (36.9%), clinical features (29.2%), and laparoscopy (27.7%); others were diagnosed by histology (3.1%) and thoracotomy (3.1%) (Table 2).
There was no statistically significant difference in IL-6 or IL-16 serum concentration between the two groups. The median serum IL-6 for the reference group, 7.61[5.81 – 12.78] pg/ml was higher than the women with endometriosis, 7.07[5.84 – 9.67] pg/ml with p-value of 0.175. A similar pattern was observed with the median serum IL-16 for the reference group, 23.17[16.39 – 45.99] pg/ml and case, 20.33[15.99 – 29.90] pg/ml groups with p-value of 0.178 (Fig. 1).
There was no statistical significance in the IL-6 serum concentration distribution according to the pain score of women with endometriosis. The median IL-6 serum concentrations was found to be 6.5 [6.4 – 8.6]pg/ml in women with endometriosis who reported mild pain, 7.1 [6.1 – 11.3]pg/ml in those who reported moderate pain, and 7.1 [5.7 – 9.3]pg/ml in those who had severe pain.
IL-16 serum distribution in women with endometriosis was significantly higher (p = 0.023) in those with severe pain (23.5[17.1 – 32.0])pg/ml compared to those who had mild pain (16.0 [16.0 – 17.8])pg/ml. IL-16 serum concentrations in women with moderate pain (17.2 [13.6 -20.9])pg/ml were not significantly different from those with mild and severe pain (Fig. 2).
IL-6 (rs1800795) was monomorphic for both the reference and the case groups. All the polymorphisms investigated in the IL-16 were in hardy–Weinberg equilibrium (p > 0.05). The minor allele frequency (MAF) of rs4778889 was significantly higher (p = 0.024) in the women with endometriosis (45%) compared to the reference group (31%) with odds ratio, 1.80 and 95% confidence interval (CI), 1.08 – 3.02. We also observed a statistical significance (p = 0.048) in the genotype frequency of rs4778889 using a recessive genetic model, further suggesting the role of rs4778889—C allele in endometriosis in Nigerian women. The distribution of genotypes and alleles of rs11556218 and rs4072111 were similar with no statistical significance (p > 0.05), (Table 3).
The observed serum IL-16 concentrations were similar across the three polymorphisms investigated in IL-16 gene (rs4778889, rs11556218, and rs4072111) in both the reference group and women with endometriosis (p > 0.05) (Table 4).
Serum IL-6 and IL-16 concentrations were similar in all the women with endometriosis, regardless of the clinical manifestation (Fig. 3).
Table 5 shows that pain score is not associated with polymorphisms studied in the IL-16 gene (p > 0.05).
Discussion
Endometriosis affects the immune system and induce proinflammatory factors, like the cytokines. Studies on IL-6 and IL-16 in women with endometriosis have been inconsistent. Some have reported significant elevated IL-6 and IL-16 concentrations in the serum and peritoneal fluid of women with endometriosis while others did not find any statistical significance [26,27,28,29]. In this study, serum IL-6 and IL-16 concentrations were not significantly different in women with endometriosis compared to those without endometriosis. Previous studies have reported an elevated serum IL-6 concentration in women with endometriosis [28, 30, 31] but one study involving Iranian women which reported higher concentration of serum IL-6 in endometriosis failed to find a significant diagnostic value for its use in identifying women with endometriosis [27].
As expected, this study found that pain-related symptoms were commonest in women with endometriosis with most affected women experiencing dysmenorrhoea and chronic pelvic pain. This explains the exploration of association between serum IL-6 and IL-16 concentration, and IL-6 and IL-16 gene polymorphisms in women with endometriosis in this study to guide further understanding on the pathogenesis of the disease and its symptoms. Another common clinical feature was ascites, usually haemorrhagic in nature, which was reported in a third of our endometriosis cases. This presentation is not commonly reported in the literature but is seen relatively frequently in our centre, probably because we are a tertiary referral centre. A systematic review found 63% of affected women to be of African descent [32].
Women with endometriosis experiencing severe pain had significantly higher IL-16 serum concentration, but there was no association between severity of pain and IL-6 serum concentration. The lack of statistical significance might be because of the small sample size in each subgroup. There is a need to further evaluate this finding in future research on a larger population of women with endometriosis. IL-16 plays a key role in inflammation [33], and pain is a hallmark of inflammation, and this may explain the association observed between serum IL-16 and severity of pain in women with endometriosis.
The rs4778889 (T/C at position -295) in the promoter region of the IL16 gene may be associated with altered concentrations of gene expression and account for the increased concentrations of IL-16 [34]. Similar to Gan et al., [21] we observed in this study that C allele of rs4778889 was associated with endometriosis suggesting its role in IL-16 gene transcription and elevated serum IL-16 concentrations.
The rs11556218 is a missense exon-SNP (T/G), located in the exon 6 region, resulting in an amino acid change (Asparagine to Lysine) on position 446 of the Pro-IL-16, which may alter protein structure–function [9]. Contrary to our findings, Greek and Iranian women with G allele of rs11556218 of IL-16 gene had increased risk of endometriosis [7, 35].
The rs4072111 is another missense SNP (C/T: Serine to Proline) located on exon 6 of IL-16 gene [9]. We did not find association between rs4072111 and endometriosis in our study like Greek and Chinese women with endometriosis [7, 21]. This is however different from the study of Azimzade et al. where T allele showed increased risk of endometriosis in Iranian women [35].
The distribution of IL-6 rs1800795 genotypes was not associated with endometriosis but CG genotype significantly correlated with serum concentration of IL-6 in women with endometriosis [36]. rs1800795 of IL-6 was monomorphic in this current study and is consistent with the data obtained from the 1000 genome browser with G allele frequency being 1.0 in 108 and 99 persons in the Yoruba in Ibadan (YRI) and the Esan (ESN) respectively from Nigerian population [37]. Gan et al. reported a variation in the frequency of 'C' allele of interleukin 6 gene to be 4.0% in Malays, 19.0% in Indians and 0.0% in Chinese living in Malaysia [38]. Lack of polymorphism of rs1800795 seen among our subjects compared to other populations underscores how genetic diversity impacts disease susceptibility.
A large multi-centre study comprising African women is desirable to elucidate the genetic polymorphisms which underpin endometriosis.
Conclusion
Our results revealed that elevated serum concentration of IL-16 was associated with pain severity and genetic polymorphism of IL-16 rs4778889 was associated with endometriosis in Nigerian women. Serum IL-16 and IL-16 rs4778889 may be important markers for endometriosis in Nigerian, and by extension, African women. A larger multicentre study in African women with endometriosis will provide further clarification.
Availability of data and materials
The datasets generated and analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.
References
Fawole A, Bello F, Ogunbode O, Odukogbe A-T, Nkwocha G, Nnoaham KE, et al. Endometriosis and associated symptoms among Nigerian women. Int J Gynaecol Obstet: Official Organ Int Fed Gynaecol Obstet. 2015;130:190–4.
Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441–7.
Méar L, Herr M, Fauconnier A, Pineau C, Vialard F. Polymorphisms and endometriosis: a systematic review and meta-analyses. Hum Reprod Update. 2020;26(1):73–102.
Fraser IS. Recognising, understanding and managing endometriosis. J Human Rep Sci. 2008;1(2):56–64.
Acién P, Velasco I. Endometriosis: a disease that remains enigmatic. ISRN Obstet Gynecol. 2013;2013:242149.
Chun S, Kim H, Ku SY, Suh CS, Kim SH, Kim JG. The association between endometriosis and polymorphisms in the interleukin-1 family genes in Korean women. Am J Reprod Immunol. 2012;68(2):154–63.
Matalliotakis M, Zervou MI, Eliopoulos E, Matalliotaki C, Rahmioglu N, Kalogiannidis I, et al. The role of IL-16 gene polymorphisms in endometriosis. Int J Mol Med. 2018;41(3):1469–76.
Lee GH, Choi YM, Kim SH, Hong MA, Oh ST, Lim YT, et al. Association of tumor necrosis factor-{alpha} gene polymorphisms with advanced stage endometriosis. Hum Reprod. 2008;23(4):977–81.
Machairiotis N, Vasilakaki S, Thomakos N. Inflammatory mediators and pain in endometriosis: a systematic review. Biomedicines. 2021;9(1):54.
Jiang J, Jiang Z, Xue M. Serum and peritoneal fluid levels of interleukin-6 and interleukin-37 as biomarkers for endometriosis. Gynecol Endocrinol. 2019;35(7):571–5.
Kokot I, Piwowar A, Jędryka M, Sołkiewicz K, Kratz EM. Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis. Int J Mol Sci. 2021;22(5):2295.
Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369–76.
Satti HS, Hussain S, Javed Q. Association of interleukin-6 gene promoter polymorphism with coronary artery disease in Pakistani families. ScientificWorldJournal. 2013;2013:538365.
Mathy NL, Scheuer W, Lanzendörfer M, Honold K, Ambrosius D, Norley S, et al. Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunology. 2000;100(1):63–9.
Chupp GL, Wright EA, Wu D, Vallen-Mashikian M, Cruikshank WW, Center DM, et al. Tissue and T Cell Distribution of Precursor and Mature IL-16. J Immunol. 1998;161(6):3114–9.
Zhang Y, Center DM, Wu DM, Cruikshank WW, Yuan J, Andrews DW, et al. Processing and activation of pro-interleukin-16 by caspase-3. J Biol Chem. 1998;273(2):1144–9.
Burkart KM, Barton SJ, Holloway JW, Yang IA, Cakebread JA, Cruikshank W, et al. Association of asthma with a functional promoter polymorphism in the IL16 gene. J Allergy Clin Immunol. 2006;117(1):86–91.
Glas J, Török HP, Unterhuber H, Radlmayr M, Folwaczny C. The -295T-to-C promoter polymorphism of the IL-16 gene is associated with Crohn’s disease. Clin Immunol. 2003;106(3):197–200.
Zhao Y, Tao L, Wang B, Nie P, Tang Y, Zhu M. Interleukin-16 gene polymorphisms rs4778889, rs4072111, rs11556218, and cancer risk in Asian populations: a meta-analysis. Genet Test Mol Biomarkers. 2014;18(3):174–82.
Liu XL, Du JZ, Zhou YM, Shu QF, Li YG. Interleukin-16 polymorphism is associated with an increased risk of ischemic stroke. Mediators Inflamm. 2013;2013:564750.
Gan XL, Lin YH, Zhang Y, Yu TH, Hu LN. Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. DNA Cell Biol. 2010;29(11):663–7.
Boonstra AM, Stewart RE, Köke AJA, Oosterwijk RFA, Swaan JL, Schreurs KMG, et al. Cut-off points for mild, moderate, and severe pain on the numeric rating scale for pain in patients with chronic musculoskeletal pain: variability and influence of sex and catastrophizing. Front Psychol. 2016;7:1466.
Rudralingam V, Footitt C, Layton B. Ascites matters. Ultrasound. 2017;25(2):69–79.
Tarn AC, Lapworth R. Biochemical analysis of ascitic (peritoneal) fluid: what should we measure? Ann Clin Biochem. 2010;47(5):397–407.
Mondry A, Loh M, Laurence KB, Low N. DNA polymorphisms and renal disease: a critical appraisal of studies presented at the annual ERA/EDTA and ASN conferences in 2004 and 2005. Nephrol Dial Transplant. 2006;21(10):2775–9.
Kang YJ, Jeung IC, Park A, Park YJ, Jung H, Kim TD, et al. An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression. Hum Reprod. 2014;29(10):2176–89.
Kashanian M, Sariri E, Vahdat M, Ahmari M, Moradi Y, Sheikhansari N. A comparison between serum levels of interleukin-6 and CA125 in patients with endometriosis and normal women. Med J Islam Repub Iran. 2015;29:280.
Li S, Fu X, Wu T, Yang L, Hu C, Wu R. Role of Interleukin-6 and Its Receptor in Endometriosis. Med Sci Monit. 2017;23:3801–7.
Koga K, Osuga Y, Yoshino O, Hirota Y, Yano T, Tsutsumi O, et al. Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis. Fertil Steril. 2005;83(4):878–82.
Wang F, Wang H, Jin D, Zhang Y. Serum miR-17, IL-4, and IL-6 levels for diagnosis of endometriosis. Medicine (Baltimore). 2018;97(24):e10853.
Wieser F, Fabjani G, Tempfer C, Schneeberger C, Sator M, Huber J, et al. Analysis of an interleukin-6 gene promoter polymorphism in women with endometriosis by pyrosequencing. J Soc Gynecol Investig. 2003;10(1):32–6.
Gungor T, Kanat-Pektas M, Ozat M, Karaca M. A systematic review: Endometriosis presenting with ascites. Arch Gynecol Obstet. 2011;283:513–8.
Schernthaner C, Paar V, Wernly B, Pistulli R, Rohm I, Jung C, et al. Elevated plasma levels of interleukin-16 in patients with acute myocardial infarction. Medicine. 2017;96(44):e8396-e.
Nakayama EE, Wasi C, Ajisawa A, Iwamoto A, Shioda T. A new polymorphism in the promoter region of the human interleukin-16 (IL-16) gene. Genes Immun. 2000;1(4):293–4.
Azimzadeh P, KhorramKhorshid HR, Akhondi MM, Shirazi A. Association of interleukin-16 polymorphisms with disease progression and susceptibility in endometriosis. Int J Immunogenet. 2016;43(5):297–302.
Wang XQ, Hu M, Chen JM, Sun W, Zhu MB. Effects of gene polymorphism and serum levels of IL-2 and IL-6 on endometriosis. Eur Rev Med Pharmacol Sci. 2020;24(9):4635–41.
Fairley S, Lowy-Gallego E, Perry E, Flicek P. The International Genome Sample Resource (IGSR) collection of open human genomic variation resources. Nucleic Acids Res. 2019;48(D1):D941–7.
Gan GG, Subramaniam R, Lian LH, Nadarajan V. Ethnic variation in interleukin-6 -174 (g/c) polymorphism in the malaysian population. Balkan J Med Genet. 2013;16(2):53–8.
Acknowledgements
Our gratitude to Sickle Cell Foundation Nigeria (SCFN) for granting assistance in specimens' storage, and to Nigerian Institution of Medical Research (NIMR), Lagos State, Nigeria for granting us the permission to use its DNA laboratory for DNA genotyping.
Funding
This research was funded by the Omololu-Mulele Grant Award of University of Lagos, Lagos State, Nigeria (Award Number VC/OA/L.09/Vol.3).
Author information
Authors and Affiliations
Contributions
OAB – Involved in the conceptualisation of research idea, participants' recruitment, laboratory analysis, data analysis and preparation of manuscript for publication. OOO—Involved in the conceptualisation of research idea, drafting of proposal, data analysis and preparation of manuscript for publication. CKO—Involved in the genetic analysis, and preparation of manuscript for publication. ICU—Involved in the drafting of proposal and preparation of manuscript for publication. AAO—Involved in the conceptualisation of research idea, provided mentorship guidance during the conduct of research and review of manuscript for publication. BBA—Involved in the conceptualisation of research idea, provided mentorship guidance during the conduct of research and review of manuscript for publication. All authors approved manuscript for publication.
Corresponding author
Ethics declarations
Ethical approval and consent to participate
The experimental protocol was approved by Lagos University Teaching Hospital Health Research and Ethics Committee (Ethical approval number: ADM/DCST/HREC/APP/2015). The research was conducted in accordance with the approved protocol. Adherence to Declaration of Helsinki on ethical principles for human subject research was ensured during conduct of this research. All participants had the autonomy to make decision regarding their participation in this research. Informed consent was signed by all women who participated in this study. Confidentiality of participants’ information was maintained.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Babah, O.A., Ojewunmi, O.O., Onwuamah, C.K. et al. Serum concentrations of IL-16 and its genetic polymorphism rs4778889 affect the susceptibility and severity of endometriosis in Nigerian women. BMC Women's Health 23, 253 (2023). https://doi.org/10.1186/s12905-023-02362-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12905-023-02362-8
Keywords
- Endometriosis
- Interleukin-6
- Interleukin-16
- Genes
- Ascites
- Genetic polymorphism
- Pain
- Nigeria