Polymorphic variants at NDUFC2, encoding a mitochondrial complex I subunit, associate with cardiac hypertrophy in...

Area of Science:

• Cardiology
• Genetics
• Mitochondrial Biology

Background:

• Mitochondrial Complex I (CI) dysfunction is implicated in left ventricular hypertrophy (LVH).
• Ndufc2, a subunit of CI, is crucial for its activity; deficiency impairs mitochondrial function.
• The T allele of NDUFC2/rs11237379 is associated with reduced NDUFC2 expression and impaired mitochondrial function.

Purpose of the Study:

• To investigate the association of NDUFC2/rs11237379 and NDUFC2/rs641836 variants with LVH in hypertensive patients.
• To explore the impact of reduced Ndufc2 expression on cardiomyocyte hypertrophy in vitro.

Main Methods:

• Genetic association analysis in 246 hypertensive patients.
• In vitro studies using H9c2 and rat primary cardiomyocytes with Ndufc2 silencing.
• Analysis of cardiac structure and function parameters.

Main Results:

• The TT genotype at NDUFC2/rs11237379 was associated with reduced NDUFC2 expression and significant differences in cardiac parameters like septal and posterior wall thickness.
• The A allele at NDUFC2/rs641836 was linked to significant differences in septal thickness, posterior wall thickness, and LV mass.
• In vitro, Ndufc2 deficiency led to cardiomyocyte hypertrophy via the SIRT3-AMPK-AKT-MnSOD signaling pathway.

Conclusions:

• NDUFC2 variants are significantly associated with LVH in human hypertension.
• Ndufc2 deficiency-driven mitochondrial dysfunction plays a key role in cardiac hypertrophy development.