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Gene & Protein in Disease                                        TNFA polymorphism and risk of endometriosis



                                                               minimize  the  effect  of multiple comparisons.  Univariate
                   HWE   (FDR)  0.63  0.35  NA  NA  0.35  0.632  0.35  0.35  0.350  logistic regression was performed to assess the association
                                                               between the genetic markers and disease risk. Odds ratios
                      HW  118  111  149  332  99  48  31       (ORs) and 95% confidence intervals (CIs) were computed
                                                               for each genetic model. For random-effects models
                   Control  HT  57  52  93  152  68  17  32    (P < 0.10), the Dersimonian and Laird method was used,
                                                               while the Mantel–Haenszel method was employed for
                      HR  5  2      6  15  6  0  4             fixed-effects models (P ≥ 0.10). In addition, the Bonferroni
                                                               correction adjusted the significance threshold from 0.05
                      HW  95  96    140  275  95  36  34       to approximately 0.0071 to better account for multiple
                                                               comparisons.
                   Case  HT  33  25  87  134  35  16  17       using Cochran’s Q test (χ²) alongside the I² statistic, with
                                                                 Heterogeneity  and  publication  bias  were  evaluated

                      HR  1  2  No data given  No data given  19  23  5  13  0  a significance threshold set at 0.10. To explore potential
                                                               biases further, both Begg’s and Egger’s tests were applied.
                                                               A  sensitivity analysis was carried out to determine the
                                                               impact of each study on the overall ORs and 95% CIs by
                   Genotyping   tech  PCR-RFLP  PCR-PHFA  PCR-RFLP  SNP-array  PCR-RFLP  HRM-PCR  PCR-RFLP  PCR-RFLP  PCR-RFLP  systematically omitting each study. Throughout all stages of
                                                               the review, the meta-analysis adhered strictly to Cochrane
                                                               guidelines. The statistical analyses were performed using
                                                               the Meta-Statistical Genyo’s Analysis System, an online tool
                   Case/  Control  129/175  123/165  210/202  958/959  246/248  432/499  135/173  65/65  51/67  specifically designed for complex genetic meta-analyses. 23
                                                                 To avoid random errors, trial sequential analysis (TSA)
                                                               was applied with a specific configuration of 80% power,
                   Source of   control  PB  HB  HB  HB  HB  HB  HB  HB  NG Abbreviations: CC: Case–control; CH: Cohort; FDR: False discovery rate; HB: Hospital based; HR: Homologous recombination; HT: Heterozygote; HW: Homozygote wild; HWE: Hardy–Weinberg  equilibrium; NA: Not available; NG: Not given; PB: Population based; PCR: Polymerase chain reaction; PHFA: Preferential homoduplex formation assay; RFLP: Restriction fragment length   20% relative risk reduction, and a
                                                               This approach enabled us to determine whether the studies
                                                               included in the meta-analysis met the required sample size
                   Type of   study  CC  CC  CC  CH  CC  CC  CC  CC  CC  criteria. 24,25

                                                               3. Result

                   Ethnicity  Asian  Asian  Asian  Caucasian  Asian  Asian  Asian  Asian  Caucasian  3.1. Meta-analysis
                                                               In the present study, we identified 18 relevant studies
                                                               through a systematic review methodology in accordance

                                                               polymorphisms of the  TNFA gene.
                                                                                                   We extracted
                                                                                            11-22,26-31
                   Country  Japan  Japan  Korea  Australia  South Korea  China  Iran  Iran  Greece  with the PRISMA guidelines (Figure 2) to explore various
                                                               a range of features from each of the 18 included studies,
                                                               focusing on TNFA variants. These features encompassed
                   YOP   2004  2004  2008  2007  2008  2012  2012  2015  2019  polymorphism; SNP: Single-nucleotide polymorphism; YOP: Year of publication.  aspects such as study design, sample size, participant
                                                               demographics, TNFA variants investigated, methodologies
                                                               employed, and genotypic data (Table 3). To ensure the
                                                               quality of the included studies, we applied the NOS.

                                                               threshold of >5 points required for inclusion, confirming
                   Authors  Asghar et al.  21  Teramoto et al.  30  Chae et al.  18  Zhao et al.  12  Lee et al.  15  Mao et al.  19  Saliminejad et al.  20  Abutorabi et al.  26  Drakou et al.  22 Note: *Indicates statistical significance (P<0.05).  Our analysis revealed that all studies met the minimum
                                                               their robustness and reliability in contributing to our
                                                               examination  of  TNFA  variants  (Table  4).  This  finding
                Table 3. (Continued)  No.  Variant  1  -1031 T>C  2  3  4  5  6  7  8  9  and analyzed in this study.
                                                               suggests a high level of confidence in the data synthesized


                                                               3.1.1. -238 G>A
                                                               For the first upstream promoter SNP,  -238 G>A, we



                                                                                            doi: 10.36922/gpd.5204
            Volume 4 Issue 3 (2025)                         5   identified six studies that investigated the relationship
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