Page 28 - GPD-4-3

Gene & Protein in Disease TNFA polymorphism and risk of endometriosis

1. Introduction 2.2. Literature survey

Women in their reproductive years often experience pelvic This study aims to establish the statistical association
pain, subfertility, and a diminished quality of life due to between various risk variants of TNFA and the likelihood
endometriosis, a complex and chronic inflammatory of developing endometriosis, utilizing a methodology
gynecological disorder characterized by the ectopic developed in alignment with the Preferred Reporting Items
presence of endometrial-like tissue outside the uterus. for Systematic Reviews and Meta-Analyses (PRISMA)
1,2
According to data from the Global Burden of Disease guidelines. Specifically, this review focused on elucidating
2019, endometriosis is considered a rare disease, with the the precise statistical associations between the following
Taiwan province of China exhibiting the highest reported risk variants: -238 G>A, -308 G>A, -850 C>T, -857
prevalence of 588.35 cases/100,000 individuals, followed C>T, -863 C>A, and -1031 T>C, and risk of endometriosis.
by New Zealand and Algeria (https://vizhub.healthdata. Data were retrieved using various scholarly search engines,
org/gbd-compare/). including Semantic Scholar, Google Scholar, and PubMed.
A combination of keywords was used, such as “rs361525
The pathogenesis of this condition is highly complex, or -238 G>A and the risk of endometriosis,” “rs1800629
involving multiple genetic factors, which categorize it or -308 G>A and the risk of endometriosis,” “-850 C>T
as a polygenic disorder. A notable example is the tumor and the risk of endometriosis,” “rs1799724 or -857 C>T
necrosis factor (TNF)-α gene, located on chromosome and the risk of endometriosis,” “-863 C>A and the risk of
6 (6p21.3), spanning approximately 3 kb and comprises endometriosis,” and “rs1799964 or -1031 T>C and the risk
four exons (Figure 1A). The TNF-alpha (TNFA) gene of endometriosis.” Significant effort was made to minimize
3
encodes a multifaceted pro-inflammatory cytokine, bias by excluding data from sources such as book chapters,
initially synthesized as a 233-amino acid transmembrane conference papers, and other unpublished or partially
protein that forms stable homotrimers (Figure 1B). Upon available writings.
proteolytic cleavage, the soluble homotrimeric TNF-α
(sTNF-α) is released and binds to TNF receptor (TNFR) 2.3. Inclusion/exclusion criteria, data extraction, and
(Figure 1C). TNF-α signaling operates through these quality assessment
receptors, influencing a range of biological activities, The studies included in the present research were selected
including inflammation, invasion, angiogenesis, and cell based on the criteria outlined in Table 2. These inclusion and
proliferation. 4,5 exclusion criteria ensure that only studies with the highest
Variations in the upstream of the TNFA gene, such relevance and quality are considered. By strictly adhering
as -238 G>A, -308 G>A, -850 C>T, -857 C>T, -863 C>A, to these criteria, we minimize potential biases, ensuring
and -1031 T>C (Table 1), have been identified, contributing that the data analyzed are both reliable and consistent,
to increased TNFA expression. These genetic variations which leads to more accurate and meaningful conclusions.
3,6
have been associated with significant disparities in This careful selection process is crucial for maintaining the
TNF-α levels observed in both serum and peritoneal integrity of the study and avoiding confounding factors
fluid. 7-10 Consequently, it is hypothesized that these that could distort the results. Following the extraction of
variations may increase susceptibility to the development data and their features (Table 3), the Newcastle–Ottawa
of endometriosis. However, research exploring this Scale (NOS) was used to evaluate the quality of the studies
relationship across different population groups has yielded (https://www.ohri.ca/home.asp). The authors involved
conflicting results. 11-22 Therefore, this meta-analysis aims in data extraction and quality assessment were A.S., S.S,
to comprehensively explore the link between the variants A.C.P, S.A.M., F.A.D., B.A.S., M.B., M.A.G., and I.A.B. Any
under study and the risk of the disease, shedding light missing data in the articles were either sourced from prior
on the role of genetic factors in this complex condition. publications or obtained by directly contacting the authors.
In addition, to ensure reliable and robust results, we Discrepancies related to article inclusion, data extraction,
thoroughly assessed the adequacy of sample sizes in our or quality assessment using the NOS were carefully
analysis. reviewed and resolved by a separate author (P.K.) to ensure
precision and consistency throughout the process.
2. Method
2.4. Statistical analysis
2.1. PROSPERO registration
Genotypic and allelic frequencies were determined for
The protocol for the ongoing review has been registered each study, and chi-square tests were used to evaluate
with the PROSPERO database under the unique the Hardy–Weinberg equilibrium (HWE). The false
registration number CRD42024527677. discovery rate approach was used to adjust P-values and

Volume 4 Issue 3 (2025) 2 doi: 10.36922/gpd.5204