Genetic Predisposition of Anti-Cytomegalovirus Immunoglobulin G Levels and the Risk of 9 Cardiovascular Diseases.

Abstract

Background:

Accumulating evidence has indicated that persistent human cytomegalovirus (HCMV) infection is associated with several cardiovascular diseases including atherosclerosis and coronary artery disease. However, whether there is a causal association between the level of anti-HCMV immune response and the risk of cardiovascular diseases remains unknown.

Methods:

Single-nucleotide polymorphisms associated with anti-cytomegalovirus immunoglobulin (Ig) G levels were used as instrumental variables to estimate the causal effect of anti-cytomegalovirus IgG levels on 9 cardiovascular diseases (including atrial fibrillation, coronary artery disease, hypertension, heart failure, peripheral artery disease, pulmonary embolism, deep vein thrombosis of the lower extremities, rheumatic valve diseases, and non-rheumatic valve diseases). For each cardiovascular disease, Mendelian randomization (MR) analyses were performed. Inverse variance-weighted meta-analysis (IVW) with a random-effects model was used as a principal analysis. In addition to this, the weighted median approach and MR-Egger method were used for further sensitivity analysis.

Results:

In the IVW analysis, genetically predicted anti-cytomegalovirus IgG levels were suggestively associated with coronary artery disease with an odds ratio (OR) of 1.076 [95% CI, 1.009-1.147; p = 0.025], peripheral artery disease (OR 1.709; 95% CI, 1.039-2.812; p = 0.035), and deep vein thrombosis (OR 1.002; 95% CI, 1.000-1.004; p = 0.025). In the further analysis, similar causal associations were obtained from weighted median analysis and MR-Egger analysis with lower precision. No notable heterogeneities and horizontal pleiotropies were observed (p > 0.05).

Conclusions/Interpretation:

Our findings first provide direct evidence that genetic predisposition of anti-cytomegalovirus IgG levels increases the risk of coronary artery disease, peripheral artery disease, and deep vein thrombosis.

• Authors: Jiang-Shan Tan, Jia-Meng Ren, Luyun Fan, Yuhao Wei, Song Hu, Sheng-Song Zhu, Yanmin Yang, Jun Cai
• Journal: Frontiers in cellular and infection microbiology (Front Cell Infect Microbiol) Vol. 12 Pg. 884298 ( 2022) ISSN: 2235-2988 [Electronic] Switzerland
• PMID: 35832381 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Tan, Ren, Fan, Wei, Hu, Zhu, Yang and Cai.

Chemical References

• Immunoglobulin G

Topics

• Cardiovascular Diseases (genetics)
• Coronary Artery Disease (genetics)
• Cytomegalovirus (genetics)
• Genetic Predisposition to Disease
• Genome-Wide Association Study (methods)
• Humans
• Immunoglobulin G
• Mendelian Randomization Analysis
• Peripheral Arterial Disease
• Polymorphism, Single Nucleotide
• Venous Thrombosis (genetics)