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Associations of dietary cholesterol consumption with incident diabetes and cardiovascular disease: the role of genetic variability in cholesterol absorption and disease predisposition

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posted on 2024-04-09, 19:15 authored by Shuxiao Shi, Ying Dong, Sujing Wang, Xihao Du, Nannan Feng, Lan Xu, Victor W. Zhong

Objective

Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear.


Research Design and Methods

DC consumption was assessed by repeated 24-hour dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n=96,826) and CVD (n=94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models.


Results

Each additional 300 mg/day of DC consumption was associated with incident diabetes (HR, 1.17 [95% CI, 1.07-1.27]) and CVD (HR, 1.09 [95% CI, 1.03-1.17]), but further adjusting for body mass index (BMI) nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90-1.09]; HR for CVD, 1.04 [95% CI, 0.98-1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction=0.04), but the stratum-level association estimates were not statistically significant.


Conclusions

DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation.

Funding

This study was supported by the National Key R&D Program of China (2022YFC2705203 and 2023YFC2506700), the National Natural Science Foundation of China (82373551), the Shanghai Key Discipline of Public Health Grants Award (GWVI-11.1-20), and the Innovative Research Team of High-Level Local Universities in Shanghai.

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