Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma

Ponomarenko, Irina; Reshetnikov, Evgeny; Полоников, А. В.; Verzilina, I.N.; Сорокина, И. Н.; Yermachenko, Anna; Dvornyk, Volodymyr; Churnosov, Mikhail

doi:10.3389/fgene.2020.512940

Cited by 51 publications

(52 citation statements)

References 79 publications

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“…The functional importance (missense replacement, eQTLs and sQTLs, regulatory potential) of the genetic variants associated with GU and those linked to them was studied in silico [ 37 , 38 ]. The SIFT online tool [ 39 ] was used to identify missense replacements and predict their functional effects.…”

Section: Methodsmentioning

confidence: 99%

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

et al. 2021

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Background and purpose The study analyzed the association of functionally significant polymorphisms of matrix metalloproteinases (MMPs) genes with the development of gastric ulcer (GU) in Caucasians from Central Russia. Methods The 781 participants, including 434 patients with GU (196 Helicobacter pylori (H. pylori)-positive and 238 H. pylori-negative) and 347 controls (all H. pylori-negative) were recruited for the study. Ten SNPs of the MMP1 (rs1799750), MMP2 (rs243865), MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs3918242, rs3918249, rs3787268, rs17576, rs17577, and rs2250889) genes were considered for association with GU using multiple logistic regression. The SNPs associated with GU and loci linked (r2≥0.8) to them were analyzed in silico for their functional assignments. Results The SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60–1.82, pperm ≤ 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85–2.04, pperm ≤ 0.016) increased risk for H. pylori-positive GU. None of the analyzed SNPs was independently associated with GU and H. pylori-negative GU. Two haplotypes of the MMP9 gene (contributed by rs3918242, rs3918249, rs17576, and rs3787268) increased risk for GU (OR = 1.62–1.65, pperm ≤ 0.006). Six loci of the MMP9 gene, which are associated with H. pylori-positive GU, and 65 SNPs linked to them manifest significant epigenetic effects, have pronounced eQTL (17 genes) and sQTL (6 genes) values. Conclusion SNPs of the MMP9 were associated with H. pylori-positive GU but not with H. pylori-negative GU in Caucasians of Central Russia.

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Section: Methodsmentioning

confidence: 99%

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

et al. 2021

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“…The polymorphisms associated with PUD and those strongly linked to them (r 2 ≥ 0.8) were analyzed for their functional significance (non-synonymous SNPs, regulatory potential, eQTLs, and sQTLs) 47 . SNPs in strong linkage disequilibrium (LD) with the PUD-associated variants were identified using HaploReg 40 .…”

Section: Methodsmentioning

confidence: 99%

Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia

Minyaylo

Ponomarenko

Reshetnikov

et al. 2021

Sci Rep

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This study analyzed the association of functionally significant SNPs of matrix metalloproteinase (MMP) genes in the development of peptic ulcer disease (PUD) in Caucasians from Central Russia. Ten SNPs of the MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 genes were analyzed for association with PUD in a cohort of 798 patients with PUD (including 404 H. pylori-positive and 394 H. pylori-negative) and 347 H. pylori-negative controls using logistic regression and assuming the additive, recessive, and dominant genetic models. The variants of MMP-1, MMP-2, MMP-3, and MMP-8 did not manifest any significant associations with the diseases. Five SNPs of the MMP-9 gene demonstrated such association. Allele G of the rs17576 MMP-9 locus conferred a higher risk for PUD (ORadj = 1.31, pperm = 0.016), haplotype AACG of loci rs17576-rs3787268-rs2250889-rs17577 of the MMP-9 gene decreased risk for PUD (ORadj = 0.17, pperm = 0.003). Also, allele C of rs3918249, allele G of rs17576 and haplotype CG of rs3918249-rs17576 of the MMP-9 gene increased risk for H. pylori-positive PUD (ORadj = 1.82, pperm = 0.002; ORadj = 1.53–1.95 pperm = 0.001–0.013 and ORadj = 1.49 pperm = 0.009 respectively). The above loci and 50 linked to them possess significant regulatory effects and may affect the alternative splicing of four genes and the expression of 17 genes in various organs and tissues related to the PUD pathogenesis.

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“…So far, reported genes associated with uLM include ODFC3, BET1L, RIC8A, SIRT3, SLK, OBFC1, TNRC6B, FASN and HMGA2; however, the specific mechanisms underlying the associations remain unclear [57]. One GWAS also associated candidate genes for age of menarche to uLM, suggesting a possible explanation for increased uLM risk in women with early menarche age [58].…”

Section: Inherited Susceptibilitymentioning

confidence: 99%

Molecular and Cellular Insights into the Development of Uterine Fibroids

Machado-Lopez

Simón

Mas

2021

IJMS

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Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.

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Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma

Cited by 51 publications

References 79 publications

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia

Molecular and Cellular Insights into the Development of Uterine Fibroids

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