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Gene & Protein in Disease Genetics of arteriovenous malformations

In this section, we discuss the potential innovative testing MicroRNA analysis through blood is another
options for SNPs analysis in saliva and microRNA analysis innovative testing option for specific genes associated with
in blood for specific genes associated with AVM. Genetic AVM. MicroRNAs are small non-coding RNA molecules
testing for AVM can be performed using various methods, that regulate gene expression by binding to messenger
including NGS, polymerase chain reaction (PCR), and RNA (mRNA) and inhibiting translation. Studies have
microarray analysis. NGS is a powerful tool that enables shown that miRNAs play a critical role in the development
the sequencing of the entire genome or specific genes of and progression of AVM [115] . Analyzing miRNA expression
interest, facilitating the identification of novel genetic patterns in blood samples can provide insights into the
variants associated with AVM [105] . On the other hand, regulatory mechanisms and potential biomarkers involved
PCR is a widely used method for detecting specific genetic in AVM. Specific miRNAs may exhibit altered expression
mutations in AVM-related genes, such as ENG, ACVRL1, levels in individuals with AVM, indicating their potential
and SMAD4, which are commonly mutated in HHT [106] . role in disease pathophysiology. Identifying miRNAs
In addition, microarray analysis can detect AVM-related associated with AVM can enhance our understanding of
genetic variations, including copy number variations and the condition’s molecular mechanisms and potentially lead
SNPs. to the development of novel diagnostic and therapeutic
strategies [116] .
Pawlikowska et al. genotyped 180 patients with bAVMs
and found that the risk of hemorrhagic presentation was Taken together, genetic testing is essential for
3-fold higher in those carrying the −174GG genotype of diagnosing and managing AVM, especially in patients
the IL-6 gene, compared with subjects carrying the CC with HHT. Innovative testing options, such as SNP analysis
and GC genotypes [80,107] . Achrol et al. tested the association through saliva and miRNA analysis through blood, offer
between two SNPs in the promoter region of the IL-6 gene non-invasive and convenient approaches for diagnosing,
(–174G > C and −572G > C) and two SNPs of the tumor predicting, and treating AVM. Further research is needed
necrosis factor alpha (TNFα) gene (–238G > A and −308G to validate the clinical utility of these testing options and
> A) with the risk of new ICH after diagnosis in 280 patients uncover novel genetic variants associated with AVM.
with bAVMs [108] . The −238G > A polymorphism of 9. Conclusion
the TNFα gene was associated with an increased risk
of bleeding during the natural course of the disease. Our understanding of the genetics mechanisms at play
Similarly, Kim et al. found that the same polymorphism in bAVM pathogenesis and growth has continued to
(–174G > C) of the IL-6 gene was associated with a 2-fold expand over the past decade. Several genes and their
increased risk of bAVM susceptibility among Latinos after downstream protein products have been implicated in
accounting for differences in ancestral background [109] . the angiogenesis and pathological formation of AVM.
Other SNPs that have been associated with AVM and ICH These discoveries have largely helped elucidate the role
include the −31T>C and −511C>T polymorphisms of the of signaling proteins, which may also affect the vascular
IL-1β gene, the −197G>A polymorphism of the IL-17A stability bAVM and ultimately result in their downstream
gene, and the −707A>G polymorphism of the MMP-3 rupture and more devastating clinical consequences. As
gene [110-112] . These SNPs can be tested for using innovative we have presented, there are a slew of genes that have been
testing options for SNPs in saliva and microRNA analysis in implicated in bAVM formation. Notably, KRAS and
in blood. These non-invasive testing options offer several IL6 have significance in sporadic bAVM phenotype. We
advantages over traditional methods of genotyping SNPs, also presented in detail the role of these genetic alteration
including reduced patient discomfort, lower costs, and in signaling pathways and targets for endothelial cellular
faster turnaround times. proliferation, migration, and angiogenesis. The emerging
treatment paradigms of AVM help stratify patient risk for
Saliva-based testing has emerged as a promising and downstream clinical consequences such as intracerebral
non-invasive approach to genetic analysis [113] . Saliva hemorrhage, seizures, and neurological deficits. However,
samples contain DNA that can be extracted and analyzed much remains to be understood about the mechanisms
for genetic variations associated with AVM. SNPs, which at play in bAVM formation. The research community
are single nucleotide changes in the DNA sequence that can has explored the use of genetic testing to evaluate
affect gene expression and protein function, are commonly interventional strategies. Further studies are needed to
detected using saliva-based testing [114] . Saliva-based testing identify genetic polymorphisms, which are associated
for SNPs associated with AVM can provide valuable with bAVM and its clinical manifestations. With
information on diagnosis, prognosis, and treatment, further studies, the exploitation of these genetic targets
allowing for personalized approaches to patient care. will hopefully result in successful improved clinical

Volume 2 Issue 2 (2023) 11 https://doi.org/10.36922/gpd.0312