Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms

Objective: The objective of this study is to determine the associations among genetic variations in the P2X7 receptor gene, decreased bone mineral density (BMD), and the risk of osteoporosis in patients aged older than 50 years with ankle fractures. Methods: Patients were genotyped for 15 nonsynonymous single-nucleotide polymorphisms (SNPs) in the P2X7 gene. The sample was divided into two groups according to the bone densitometry results: an intervention group with osteopenia (T scores between –1.0 and –2.5) or osteoporosis (T scores ≤ –2.5) and a control group with values within the normal range (T scores ≥ –1). A total of 121 patients were evaluated: 65 in the intervention group and 56 in the control group. Results: The results suggested that SNPs 1, 4, 11, 13, 14, and 15 were loss-of-function (LOF) variants. SNP 12 was also associated with LOF in our population, but its RNA expression has not been analyzed to date. Conclusions: In conclusion, we demonstrate that functional polymorphisms in P2X7 are associated with BMD and with an increased risk of ankle fractures. The limitations of our study are its focus on nonsynonymous polymorphisms, which do not cover all genetic variations in P2X7, and its small sample size compared with the international literature. A strength of this study is that it is the first to evaluate P2X7 in the Brazilian population.

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Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures

European Journal of Human Genetics ◽

10.1038/ejhg.2011.253 ◽

2012 ◽

Vol 20 (6) ◽

pp. 675-681 ◽

Cited By ~ 52

Author(s):

Niklas R Jørgensen ◽

Lise B Husted ◽

Kristen K Skarratt ◽

Leanne Stokes ◽

Charlotte L Tofteng ◽

...

Keyword(s):

Bone Loss ◽

Single Nucleotide Polymorphisms ◽

Vertebral Fractures ◽

P2x7 Receptor ◽

Receptor Gene ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Post Menopausal

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Effect of non-synonymous single nucleotide polymorphisms in rho domain of TAGAP: structural modeling and molecular dynamics simulation approach

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2020.sp1.329 ◽

2020 ◽

Vol 12 (sp1) ◽

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Single Nucleotide Polymorphisms ◽

Structural Modeling ◽

Dynamics Simulation ◽

Nucleotide Polymorphisms ◽

Simulation Approach ◽

Single Nucleotide

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Hypoxia-inducible factor: analysis of the HIF1A and HIF1B single nucleotide polymorphisms and their functional role in development of uterine fibroids

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.06.49-51 ◽

2020 ◽

pp. 49-51

Author(s):

Е.М. Барышева ◽

С.М. Зайцев ◽

Н.В. Горяинова ◽

Л.А. Пономарева ◽

О.Б. Полшведкина ◽

...

Keyword(s):

Factor Analysis ◽

Single Nucleotide Polymorphisms ◽

Protective Effect ◽

Functional Role ◽

Molecular Mechanisms ◽

Hypoxia Inducible Factor ◽

Uterine Fibroids ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

В исследование были включены 584 пациентки с миомой матки и 391 женщина контрольной группы. Генотипирование однонуклеотидных полиморфизмов (SNP) генов HIF1A и HIF1B (rs2301106, rs2301113, rs1951695, rs2057482, rs4899056 HIF1A и rs3738493, rs10847 HIF1B) было проведено методом ПЦР в режиме реального времени. Выявлен протективный эффект rs10847 HIF1B относительно риска развития миомы матки (OR=0,78, 95%CI=0,63-0,95; p=0,016). Обсуждаются молекулярные механизмы связи rs10847 HIF1B с патогенезом миомы матки. A total of 584 patients with uterine fibroids and 391 healthy controls were recruited for the study. Genotyping of single nucleotide polymorphisms (SNPs) of the HIF1A and HIF1B genes (rs2301106, rs2301113, rs1951695, rs2057482, rs4899056 HIF1A and rs3738493, rs10847 HIF1B) was performed using real-time PCR). The protective effect of rs10847 HIF1B against the risk of uterine fibroids was revealed (OR=0.78, 95%CI=0.63-0.95; P=0.016). The molecular mechanisms of the involvement of rs10847 HIF1B to the pathogenesis of uterine fibroids are discussed.

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