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A Potential Strategy for Atherosclerosis Prevention in Modernizing China — Hyperhomocysteinemia, MTHFR C677T Polymorphism and Air Pollution (PM2.5) on Atherogenesis in Chinese Adults

  • Original Research
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The journal of nutrition, health & aging

Abstract

Background

Atherosclerosis is one of the most important global health hazards and air pollution (AP, PM2.5) has been implicated. In addition to traditional risk factors hyperhomocysteinemia (HC) has been recognized in many parts of China related to risk of stroke.

Methods

To evaluate the impact of HC (homocysteine >14µmol/l) and PM2.5 air pollution on atherogenesis in modernizing China, we studied 756 asymptomatic Chinese in China from 1998–2007. PM2.5 exposure, HC, folate, and methylenetetrahydrofolate reductase (MTHFR) C/T genotype were evaluated. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. Locations were categorized as zones 1, 2 and 3, with increasing PM2.5 exposure.

Results

HC was higher (19.4±13.1 and 27.1±25.1µmol/l) in high PM2.5-polluted zones 2 and 3 than in zone 1 (9.7±4.5µmol/l, p<0.0015). The top HC tertile was characterized by lower folate and vitamin B12, but a higher proportion of the MTHFR TT genotype, Metabolic Syndrome (MS) and PM2.5 level (p=0.0018). FMD was significantly lower (7.3±2.3%) and carotid IMT thicker (0.63±0.12mm) in the top HC tertile, compared with low HC tertile (8.4±2.5%, p<0.0001; 0.57±0.1mm, p<0.0001 respectively). Similar differences in FMD and IMT were seen in zones 2 and 3, compared with zone 1 (p<0.0001). On multivariate regression, HC was related to male gender (beta=0.106, p=0.021), MTHFR-TT (beta=0.935, p<0.0001), locations (beta=0.230, p<0.0001) and folate-MTHFR interaction (beta=−0.566, p<0.0001). FMD was related to age (beta= −0.221; p<0.0001), male gender (beta= −0.194, p=0.001) PM2.5 and location (beta=−0.285 to −0.303, p<0.0001). Carotid IMT was related to PM2.5 (beta=0.173, p<0.0001), HC (0.122, p=0.006) but not to MTHFR or location, independent of age, gender, MS, and LDL-C. No significant HC-PM2.5 interaction effect on FMD and IMT was observed.

Conclusion

HC and PM2.5 pollution but not MTHFR genotype were both related to carotid IMT, independent of other traditional risk factors. This has potential implications in dietary and AP strategies for atherosclerosis prevention in China.

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Data Availability Statement

The research data will be available from the corresponding author to the editor and Atmosphere readers on reasonable request.

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Acknowledgments

We wish to acknowledge the valuable support of the Chinese Atherosclerosis Trust, Leung Kit Wah Project Fund, Stanley Ho Medical Development Foundation Trust, The Star Industrial Company Fund of The Chinese University of Hong Kong and Thomas HC Cheung Trust in sponsoring the study. We also acknowledge The Macau Heart Foundation, for helping recruitment of subjects, and the Pathology Department of Centro Hospitalar Conde de Sao Januario in Macau for the blood assays. We acknowledge the superb statistical analyses and clerical work of Mikki Wong and Daphne Pui Yan Chu, of The Chinese University of Hong Kong.

Funding

This work was supported by The Chinese Atherosclerosis Trust, Madam Leung Kit Wah Project Fund, Dr Stanley Ho Medical Development Foundation (grant and donation), Star Industrial Company and Dr Thomas HC Cheung Trust: They provided unrestricted sponsorships for the present study, without any involvement in study design, data collection, analysis or interpretation, nor in the writing of this report or the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Medicine and Therapeutics, United College, The Chinese University of Hong Kong, Tsang Shiu Tim Building, Shatin NT, Hong Kong SAR, China

    C. Y. T. Kwok, Y. K. P. Poon, P. Chook & K. S. Woo

  2. Department of Medicine, Yu County Provincial Hospital, Zhangjiakou, China

    D. S. Guo

  3. Division of Environment and Sustainability, The Hong Kong University of Science and Technology, Hong Kong SAR, China

    C. Q. Lin

  4. Department of Cardiology, Second Hospital of Chongqing Medical University, Chongqing, China

    Y. H. Yin

  5. Faculty of Medical and Health Science, The University of Sydney, Sydney, Australia

    D. S. Celermajer

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  1. C. Y. T. Kwok
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Contributions

Kwok CY, Timothy: Design of project, interpretation of data, revision of the article and final approval of the version to be published. Poon YK Peter: Statistical analysis (MTHFR — C677T) and interpretation of data, revision of the article and final approval of the version to be published. Chook Ping: Project conception and design, performance of ultrasonography analysis and interpretation of data, drafting, revision of the article and final approval of the version to be published. Guo DS: Project conception, analysis and interpretation of data, revision of the article and final approval of the version to be published. Yin YH: Project conception, interpretation of data, revision of the article and final approval of the version to be published. Lin CQ: Provision and interpretation of PM2.5 data in China, revision of the article and final approval of the version to be published. Celermajer DS: Project conception and design, interpretation of data, drafting and revision of the article, and final approval of the version to be published. Woo KS: Project conception and design, research administration, statistical analysis and interpretation of data, drafting and revision of the article and final approval of the version to be published. All authors agree to be accountable for all aspects of the works. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to K. S. Woo.

Ethics declarations

Our experiments comply with the current laws of the Peoples’ Republic of China in which they were performed. We agree upon standards of expected ethical behavior for all parties involved in the act of publishing: the Authors, the Editorin- Chief, the Peer-Reviewers and the Publisher, based on COPE’s Best Practice Guidelines for Journal Editors and on the International Committee of Medical Journal Editors (ICMJE) recommendations. The JNHA devotes special attention to detect any plagiarism overlapping publications.

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Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki (1995 & 2003), and the research protocol and written informed consent form were approved by the Institutional Review Board at the Chinese University of Hong Kong in 2018 (CREC 2018.157).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Disclosure Statement

Timothy CY Kwok: Declares no Conflict of Interest; Poon YK Peter: Declares no Conflict of Interest; Chook P: Declares no Conflict of Interest; Guo DS: Declares no Conflict of Interest; Lin CQ: Declares no Conflict of Interest; Yin YH: Declares no Conflict of Interest; Celermajer DS: Declares no Conflict of Interest; Woo KS: Declares no Conflict of Interest.

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Kwok, C.Y.T., Poon, Y.K.P., Chook, P. et al. A Potential Strategy for Atherosclerosis Prevention in Modernizing China — Hyperhomocysteinemia, MTHFR C677T Polymorphism and Air Pollution (PM2.5) on Atherogenesis in Chinese Adults. J Nutr Health Aging 27, 134–141 (2023). https://doi.org/10.1007/s12603-023-1889-x

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