PLCH2 gene modifies the U-shaped association between environmental selenium exposure and blood total cholesterol: A gene-environment interaction study.

Exposure to excessive selenium (Se) is hazardous to human health, while Se is also an essential trace element. Therefore, exploring the appropriate exposure dose of Se has received widespread attention. Currently, the impact of Se exposure on blood lipids remains uncertain, and the potential mechanism is still unclear. Evidence from our earlier study pointed to PLCH2 as a potentially pivotal element in the association between Se exposure and total cholesterol (TC). This study aims to explore the appropriate exposure dose of Se on blood lipids, and effects of PLCH2 gene on the relationship between Se exposure and blood lipids through a longitudinal epidemiological study. Repeated measurements of urinary Se (Se-U) for 6260 participants with 9347 observations from the Wuhan-Zhuhai cohort were performed, and a U-shaped relationship between Se-U and TC was observed, the turning point of Se-U was 2.229 μg/mmol Cr. When lower than the turning point, Se-U was negatively associated with TC, while higher than the turning point, Se-U was positively associated with TC. Then, 2985 participants (6026 observations) were genotyped, and all 109 single-nucleotide polymorphisms (SNPs) within PLCH2 gene were included. Significant interaction (Pint<0.05) was observed between a haplotype of the PLCH2 and Se-U on TC: the U-shaped relationship was still observed in the PLCH2-ATCTCA haplotype carriers but not in the haplotype non-carriers. The results suggested PLCH2 gene can modify the U-shaped relationship between Se exposure and TC, which showed a new gene-environment interaction and will provide a new perspective on the relationship between Se exposure and TC.