SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases

Area of Science:

• Genetics and Molecular Biology
• Cardiology
• Biochemistry

Background:

• Cardiovascular disease (CVD) is a leading global cause of mortality, influenced by gene-environment interactions and epigenetic factors.
• SIRT1 protein plays a crucial role in maintaining homeostasis and protecting against CVD-related damage.
• Epigenetic modifications, including single nucleotide polymorphisms (SNPs), are increasingly recognized as contributors to CVD pathogenesis.

Purpose of the Study:

• To investigate the association between specific SIRT1 gene polymorphisms (rs7895833, rs7069102, rs2273773) and CVD.
• To examine the correlation of these SIRT1 SNPs with SIRT1 and eNOS protein expression levels.
• To assess the relationship between SIRT1 SNPs and markers of oxidative stress: total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in CVD patients.

Main Methods:

• Genotyping of three SIRT1 SNPs (rs7895833, rs7069102, rs2273773) in CVD patients and control subjects.
• Measurement of SIRT1 and eNOS protein expression levels using relevant biochemical assays.
• Quantification of TAS, TOS, and OSI to evaluate oxidative stress status.

Main Results:

• Mutant genotypes and alleles for rs7069102 and rs2273773 were significantly more frequent in CVD patients, indicating a 2.4-fold and 1.9-fold increased CVD risk, respectively, associated with their mutant alleles.
• No significant association was found for rs7895833 SNP with CVD.
• CVD patients exhibited elevated SIRT1 protein, TAS, TOS, and OSI, but reduced eNOS protein levels compared to controls.
• Increased SIRT1 expression was observed in CVD patients with the mutant genotype for rs7069102 and heterozygote genotypes for all three SNPs.

Conclusions:

• SIRT1 gene polymorphisms, specifically rs7069102 and rs2273773, are associated with an increased risk of cardiovascular disease.
• These genetic variations correlate with altered SIRT1 and eNOS protein expression and dysregulated oxidative stress markers in CVD patients.
• This study provides novel insights into the interplay between SIRT1 genetics, protein expression, and oxidative stress in the context of cardiovascular disease.