XRCC3 polymorphism is associated with hypertension-induced left ventricular hypertrophy

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Cell Biology

Background:

• X-ray repair cross-complementing protein 3 (XRCC3) is crucial for DNA repair.
• The XRCC3 241Met variant is linked to endoreduplication and polyploidy.
• Hypertension-induced left ventricular hypertrophy (LVH) is a significant cardiovascular complication.

Purpose of the Study:

• To investigate the association between the XRCC3 Thr241Met polymorphism and hypertension-induced LVH.
• To elucidate the cellular and molecular mechanisms linking XRCC3 polymorphism to LVH.

Main Methods:

• Genotyping of XRCC3 Thr241Met polymorphism in hemodialysis patients (n=77).
• Introduction of XRCC3 cDNA variants (241Thr, 241Met) into cultured cells (CHO, NIH3T3).
• Assessment of DNA damage, cell cycle progression, senescence, and inflammatory markers (MCP-1).

Main Results:

• The XRCC3 241Thr/Met genotype was more frequent in patients with LVH.
• XRCC3 241Met expression increased cell size, DNA double-strand breaks, and polyploidy.
• Cells expressing 241Met showed increased senescence and higher MCP-1 mRNA/protein levels.
• MCP-1 levels correlated positively with polyploidy and G2/M phase cell percentage.

Conclusions:

• The XRCC3 241Met polymorphism is associated with an increased risk of LVH in hemodialysis patients.
• This variant promotes LVH through DNA damage accumulation, altered cell cycle, senescence, and inflammation.
• XRCC3 genotype may represent a novel risk factor for cardiovascular remodeling.