Association of IGF-1 CA(n) and IGFBP3 rs2854746 Polymorphisms with Endometrial Polyp Risk

Abstract

Introduction Insulin-like growth factor 1 (IGF-1) is a peptide growth factor that promotes cell proliferation and inhibits apoptosis. The bioavailability of IGF-1 is regulated by the insulin-like growth factor binding protein 3 (IGFBP3). Genetic variations influence the levels of IGF-1 and IGFBP3. The purpose of this study was to examine the association of polymorphisms IGF-1 CA(n) and IGFBP3 rs2854746 with risk of endometrial polyps. Materials and Methods Case control observational study, composed of 104 women with antecedent of endometrial polyp (case group) and 81 postmenopausal women without antecedent of endometrial diseases (control group). Genotyping of IGF-1 CA(n) was performed by PCR and fragment analysis by capillary electrophoresis, and genotyping of IGFBP3 rs2854746 was performed by PCR-HRM. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Results The genotype IGF-1 CA(19)/CA(19) was associated with an increased endometrial polyp risk (OR=2,57; IC 95%= 1,09 - 6,01); this was also found when combining it with CA(>19)/CA(n) genotypes (OR=2,18; IC 95%= 1,06-4,47). The IGFBP3 rs2854746 analyses showed the CG genotype having a protective effect for endometrial polyp (OR=0,37; IC 95%= 0,19-0,73), fact also observed when grouping CG and GG carriers (OR=0,51; IC 95%= 0,28-0,93). Conclusion The genotypes CA(19)/CA(19) and CA(19)/CA(19) + CA(>19)/CA(n) of the IGF-1 CA(n) may be considered a risk for endometrial polyp, whereas the genotypes CG and CG + GG of IGFBP3 rs2854746 polymorphism have an inverse effect of endometrial polyp risk.

The regulation of IGFBP3 by BMP2 has a role in human endometrial remodeling

“…46 Intriguingly, ID1 has been shown to mediate TGF-β-induced MET in a metastatic colonization model, and this effect is controlled by a mesenchymal marker, Snail1. 47 Data obtained from clinical studies have demonstrated a significant association between the dysregulation of IGFBP3 and several reproduction-related pathological conditions, including endometriosis, 17 endometrial polyps, 48 and intrauterine growth retardation. 49 Previous studies showed that IGFBP3 is upregulated during the invasive differentiation of cytotrophoblasts.…”

The role of genetic disorders in the formation of disabling effects in the premature newborn

“…Этот полиморфизм влияет на концентрацию свободно циркулирующего белка-3, связывающего инсулиноподобный фактор роста. Выявленный у пациента генотип СС c.C95G IGFBP3 связан с низкими концентрациями циркулирующего IGFBP-3, что делает фактор роста IGF-1 более эффективным и ускоряет рост клеток [20].…”

Large-scale genome-wide association study to determine the genetic underpinnings of female genital tract polyps

“…However, it can be assumed that the development and mechanism of polyps are multifactorial and can also depend on genetic predisposition. Thus far, the proposed genetic mechanisms are primarily based on small candidate gene studies and are inconclusive (Altaner et al ., 2006; Pal et al ., 2008; Banas et al ., 2018; Doria et al ., 2018; Takeda et al ., 2019). Studies in other complex diseases have shown that genome-wide association studies (GWAS) can provide valuable insight into disease biology (Claussnitzer et al ., 2016), but as far as we are aware, no large-scale GWAS have been published for FGT polyps.…”