Single-nucleotide polymorphism rs10036727 in the <i>SLIT3</i> gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women

Hidalgo‐Bravo, Alberto; Hernández-Medrano, Cristina; Sevilla‐Montoya, Rosalba; Rivera‐Paredez, Berenice; Ramírez‐Salazar, Eric G.; Flores-Morales, Jeny; Patiño, Nelly; Salmerón, Jorge; Valdés-Flores, Margarita; Velázquez‐Cruz, Rafael

doi:10.1080/09513590.2020.1804548

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…In contrast, our results shown that variant rs6086746 was associated with higher BMD and protective effect against low-BMD in women aged 45 years or older. These results are consistent with an independent group of OP patients from the National Institute of Rehabilitation (INR) in Mexico City ( 36 ). Although the frequencies were similar in both cohorts, we did not observe statistical differences (OR = 0.74, 95%CI 0.47-1.16), perhaps due to the small sample size (n=384).…”

Section: Discussionsupporting

confidence: 88%

“…Genetic variants in PLCB4 have been identified as cause of the Auriculocondylar syndrome 2 (ARCND2), a disease characterized by craniofacial malformations (13), PLCB4 acts as a direct signaling effector of the endothelin receptor type A (EDNRA)-Gq/11 pathway. Kanai et al, 2022 demonstrated that variants in PLCB4 gene interfere with the EDNRA signaling pathway, leading to the development of ARCND2 (35). However, the role of genetic variants in PLCB4 on BMD has been explored only to a limited extent.…”

Section: B C Amentioning

confidence: 99%

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Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women

Aparicio-Bautista,

Jiménez-Ortega,

Becerra-Cervera

et al. 2024

Front. Endocrinol.

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IntroductionUnderstanding the genetic factors contributing to variations in bone mineral density (BMD) and vitamin D could provide valuable insights into the pathogenesis of osteoporosis. This study aimed to evaluate the association of single nucleotide variants in MARK3 (rs11623869), PLCB4 (rs6086746), and GEMIN2 (rs2277458) with BMD in Mexican women.MethodsThe gene-gene interaction was evaluated in these variants in serum 25(OH)D levels and BMD. A genetic risk score (GRS) was created on the basis of the three genetic variants. Genotyping was performed using predesigned TaqMan assays.ResultsA significant association was found between the rs6086746-A variant and BMD at the total hip, femoral neck, and lumbar spine, in women aged 45 years or older. However, no association was observed between the variants rs11623869 and rs2277458. The rs11623869 × rs2277458 interaction was associated with total hip (p=0.002) and femoral neck BMD (p=0.013). Similarly, for vitamin D levels, we observed an interaction between the variants rs6086746 × rs2277458 (p=0.021). GRS revealed a significant association with total hip BMD (p trend=0.003) and femoral neck BMD (p trend=0.006), as well as increased vitamin D levels (p trend=0.0003). These findings provide evidence of the individual and joint effect of the MARK3, PLCB4, and GEMIN2 variants on BMD and serum vitamin D levels in Mexican women.DiscussionThis knowledge could help to elucidate the interaction mechanism between BMD-related genetic variants and 25OHD, contributing to the determination of the pathogenesis of osteoporosis and its potential implications during early interventions.

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Section: Discussionsupporting

confidence: 88%

Section: B C Amentioning

confidence: 99%

Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women

Aparicio-Bautista,

Jiménez-Ortega,

Becerra-Cervera

et al. 2024

Front. Endocrinol.

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“…It is characterized by low bone mass and microarchitecture deterioration, resulting in fragile bones and thus increasing the probability of fracture. , Diagnosis of osteoporosis is typically achieved by measuring the bone density by dual-energy X-ray absorptiometry and monitoring bone density at periodic intervals over a 2–3 year time frame . Recent reports have identified SNPs that are associated with an increased risk of bone fracture and can be used as markers of an increased risk of bone-fracture and as markers of a predisposition to osteoporosis. − …”

Section: Introductionmentioning

confidence: 99%

“… 44 Recent reports have identified SNPs that are associated with an increased risk of bone fracture and can be used as markers of an increased risk of bone-fracture and as markers of a predisposition to osteoporosis. 45 − 48 …”

Section: Introductionmentioning

confidence: 99%

Semiautomated Electrochemical Melting Curve Analysis Device for the Detection of an Osteoporosis Associated Single Nucleotide Polymorphism in Blood

Yenice,

Chahin,

Jauset-Rubio

et al. 2023

Anal. Chem.

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The detection of single nucleotide polymorphisms (SNPs) is of increasing importance in many areas including clinical diagnostics, patient stratification for pharmacogenomics, and advanced forensic analysis. In the work reported, we apply a semiautomated system for solid-phase electrochemical melting curve analysis (éMCA) for the identification of the allele present at a specific SNP site associated with an increased risk of bone fracture and predisposition to osteoporosis. Asymmetric isothermal recombinase polymerase amplification using ferrocene labeled forward primers was employed to generate single stranded redox labeled amplicons. In a first approach to demonstrate the proof of concept of combining asymmetric RPA with solid-phase éMCA, a simplified system housing a multielectrode array within a polymeric microsystem, sandwiched between two aluminum plates of a heater device, was used. Sample manipulation through the microfluidic channel was controlled by a syringe pump, and an external Ag/AgCl reference electrode was employed. Individual electrodes of the array were functionalized with four different oligonucleotide probes, each probe equivalent in design with the exception of the middle nucleotide. The isothermally generated amplicons were allowed to hybridize to the surface-tethered probes and subsequently subjected to a controlled temperature ramp, and the melting of the duplex was monitored electrochemically. A clear difference between the fully complementary and a single mismatch was observed. Having demonstrated the proof-of-concept, a device for automated éMCA with increased flexibility to house diverse electrode arrays with internal quasi-gold reference electrodes, higher resolution, and broader melting temperature range was developed and exploited for the detection of SNP hetero/homozygosity. Using the optimized conditions, the system was applied to the identification of the allele present at an osteoporosis associated SNP site, rs2741856, in 10 real fingerprick/venous blood samples, with results validated using Sanger sequencing.

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SLIT3-mediated fibroblast signaling: a promising target for antifibrotic therapies

Gong,

2023

American Journal of Physiology-Heart and Circulatory Physiology

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The SLIT family (SLIT1-3) of highly conserved glycoproteins were originally identified as ligands for the Roundabout (ROBO) family of single-pass transmembrane receptors, serving to provide repulsive axon guidance cues in the nervous system. Intriguingly, studies involving SLIT3 mutant mice suggest that SLIT3 might have crucial biological functions outside the neural context. While these mutant mice display no noticeable neurological abnormalities, they present pronounced connective tissue defects, including congenital central diaphragmatic hernia, membranous ventricular septal defect, and osteopenia. We recently hypothesized that the phenotype observed in SLIT3-deficient mice may be tied to abnormalities in fibrillar collagen-rich connective tissue. Further research by our group indicates that both SLIT3 and its primary receptor, ROBO1, are expressed in fibrillar collagen-producing cells across various non-neural tissues. Global and constitutive SLIT3 deficiency not only reduces the synthesis and content of fibrillar collagen in various organs but also alleviates pressure overload-induced fibrosis in both the left and right ventricles. This review delves into the known phenotypes of SLIT3 mutants and the debated role of SLIT3 in vasculature and bone. Present evidence hints at SLIT3 acting as an autocrine regulator of fibrillar collagen synthesis, suggesting it as a potential anti-fibrotic treatment. However, the precise pathway and mechanisms through which SLIT3 regulates fibrillar collagen synthesis remain uncertain, presenting an intriguing avenue for future research.

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Single-nucleotide polymorphism rs10036727 in the SLIT3 gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women

Cited by 5 publications

References 20 publications

Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women

Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women

Semiautomated Electrochemical Melting Curve Analysis Device for the Detection of an Osteoporosis Associated Single Nucleotide Polymorphism in Blood

SLIT3-mediated fibroblast signaling: a promising target for antifibrotic therapies

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