Evaluation of the fibulin 5 gene polymorphism as a factor related to the occurrence of pelvic organ prolapse

Paula, Marcus Vinicius Barbosa de; Júnior, Marcos Antônio de Farias Lira; Monteiro, Vivian Costa E Silva Crocco; Souto, Ricardo Peres do; Fernandes, César Eduardo; Oliveira, Emerson

doi:10.1590/1806-9282.66.5.680

Cited by 5 publications

(2 citation statements)

References 18 publications

(14 reference statements)

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“…FBLN5 has been investigated as a candidate gene for prolapse as fibulins play a critical role in the assembly of elastic fibers, believed to provide strength and flexibility in the pelvic floor. Three studies from Brazil, Russia, and China assessed the same two variants (rs2018736 and rs12589592) of which two studies could be included in meta-analyses [ 19 , 21 , 22 ]. No significant pooled effect was observed for rs2018736, but a large effect was seen at rs12589592 with moderate heterogeneity (OR 1.43 95% CI 1.11–1.82, I 2 = 36.3%, Venice rating BBB).…”

Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse

et al. 2021

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Introduction and hypothesis Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations. Methods Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria. Results We screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at the ESR1 gene (OR 0.67 95% CI 0.46–0.98, I2 = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11–1.82, I2 = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39–0.96, I2 = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66–0.96, I2 = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies. Conclusion The genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse

et al. 2021

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“…The aforementioned results demonstrated that the ESR1 genotype may be a predisposing factor for POP and that it may be used as a potential therapeutic target for this disease. Apart from the aforementioned genes (COL3A1 rs1800255; COL1A1 rs1800012; ESR1 rs2228480), other genes involved in the occurrence and development of POP have been discovered, including MMP1, laminin γ-1 rs10911193, progesterone receptor rs484389, LOXL1 and common SNPs of the FBLN5 gene (rs2018736, rs12589592) (48,(51)(52)(53)(54)(55)(56). In addition, genome-wide association studies have determined that the presence of chromosomes 9q21, 10q24-26 and 17q25 is associated with the susceptibility of European patients with POP (57-59).…”

Section: Genetic Susceptibility and Popmentioning

confidence: 99%

Advances in molecular mechanisms of pelvic organ prolapse (Review)

et al. 2021

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Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed. Contents

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