Multiple plasma metals, genetic risk and serum complement C3, C4: A gene-metal interaction study

Area of Science:

• Environmental Health
• Immunology
• Toxicology

Background:

• Metals and metalloids exposure is linked to human health and immune system function.
• The complement system, particularly C3 and C4, is crucial in immunity and inflammatory diseases.
• Limited research exists on the relationship between multiple metals and complement levels.

Purpose of the Study:

• To investigate the association between 17 plasma metals and serum C3, C4 levels in a Chinese cohort.
• To calculate C3/C4-associated genetic risk scores (GRSs) and explore gene-metal interactions.
• To understand the impact of metal exposure on the human immune system.

Main Methods:

• Analysis of 2977 participants from the Dongfeng-Tongji cohort.
• Measurement of 17 plasma metals and serum C3, C4 levels.
• Calculation of C3/C4-GRSs using established single nucleotide polymorphisms.

Main Results:

• Increased plasma copper was associated with higher serum C3 and C4 levels.
• Increased plasma zinc showed a marginal association with higher C3 levels.
• A significant interaction was found between arsenic exposure and C3-GRS for C3 levels.

Conclusions:

• Plasma copper and zinc levels are associated with complement components C3 and C4.
• Arsenic exposure may modify the relationship between C3 genetic predisposition and serum C3 levels.
• Findings provide new insights into metal exposure effects on the human immune system, warranting further research.