On August 12, 2020,  for the first time, Prof. LIN Xu's research group at the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences has shown the interaction effect of genetic risk score (GRS) of cholesterol and dietary cholesterol intake on blood cholesterol levels.

According to a report which pooled 102.6 million adults from 200 countries, the estimated high non-HDL-cholesterol (non-HDL-C) accounted for 3.9 million global deaths in 2017 and half of the death was in Asian countries. Cholesterol in human body comes approximately 30% attributing to dietary intake and about 70% from de novo synthesis in the liver. The responsiveness of blood cholesterol profile toward dietary cholesterol intake varied considerably between different populations and individuals.

Most available studies conducted in western populations only investigated effects of individual SNPs with minor influences. Though many genes involve in the complex regulation on maintaining cholesterol homeostasis, few studies have systematically evaluated collective effects of multiple genetic variants on the relationships between dietary cholesterol intake and plasma cholesterol.

Thus, by constructing GRSs which combining multiple genetic variants, the researchers aimed to examine the accumulative effects of multiple genetic variants and their interaction with dietary cholesterol intake on plasma cholesterol levels in a Chinese population. 

In this study, under supervision of Prof. LIN Xu and Prof. LI Huaixing, Ph.D. candidate HUO Shaofeng established GRSs for total cholesterol (TC) (GRS_TC, 57 SNPs) and LDL-C (GRS_LDL-C, 45 SNPs) in 2,330 participants. These participants were from the baseline of the Nutrition and Health of Aging Population in China study, which aimed to investigate genetic and environmental risk factors and their interaction in metabolic diseases.

The researchers found that increased dietary cholesterol intake was significantly associated with elevated plasma TC, LDL-C and non-HDL-C levels.

Results also revealed that GRS_TC and GRS_LDL-C were positively associated with circulating levels of TC and LDL-C, respectively.

Moreover, at given levels of dietary cholesterol, individuals with higher GRS_TC or GRS_LDL-C had higher plasma TC, LDL-C or non-HDL-C levels than their counterparts with lower GRSs.

In addition, the  discovered that the effect of GRS_TC or GRS_LDL-C on plasma TC or LDL-C levels were more pronounced among those participants with higher consumption of dietary cholesterol.  

Overall, this study provides important evidence regarding to personalized recommendation for dietary cholesterol intake and also demonstrated potential application of genetic risk score in precision nutrition.  

 This study was online published in Journal of Lipid Research entitled "Genetic Susceptibility, Dietary Cholesterol Intake and Plasma Cholesterol Levels in a Chinese Population".

This study was funded by the Major Project of the Ministry of Science and Technology of China, the Strategic Priority Research Program of Chinese Academy of Sciences and the National Natural Science Foundation of China.