Single Nucleotide Polymorphism of TWIST2 May Be a Modifier for the Association between High-Density Lipoprotein Cholesterol and Blood Lead (Pb) Level

The association between lead (Pb) exposure and lower high-density lipoprotein cholesterol (HDL-C) was reported; however, the mechanism was unclear. Our purpose was to investigate the association of Pb, lipid profile, and to study the associated SNPs using a genome-wide association study (GWAS). A total of 511 participants were recruited to check blood Pb levels, lipid profile, and genotypes with Taiwan Biobank version 2.0 (TWB2). Our main result shows that HDL-C was significantly negatively associated with blood Pb levels, adjusted for gender, body mass index (BMI), and potential confounders. In addition, via the TWB2 GWAS, only two SNPs were found, including rs150813626 (single-nucleotide variation in the TWIST2 gene on chromosome 2), and rs1983079 (unclear SNP on chromosome 3). Compared to the rs150813626 GG carriers, the AA and AG carriers were significantly and negatively associated with HDL-C. We analyzed the interaction of rs150813626 SNP and blood Pb, and the HDL-C was consistently and negatively associated with blood Pb, male, BMI, and the rs150813626 AA and AG carriers. Moreover, the rs150813626 AA and blood Pb interaction was significantly and positively associated with HDL-C. In conclusion, the SNPs rs150813626 and rs1983079 were significantly associated with HDL-C in Pb-exposed workers. Furthermore, the interaction of rs150813626 AA and blood Pb had a positive influence on HDL-C. TWIST may inhibit osteoblast maturation, which might relate to bone Pb deposition and calcium metabolism. The mechanism needs more investigation in the future.

Automated summary

This study found a negative association between lead exposure and high-density lipoprotein cholesterol (HDL-C) levels. Two specific SNPs were significantly associated with HDL-C in lead-exposed workers, and an interaction between one of the SNPs (rs150813626) and lead exposure had a positive influence on HDL-C. The TWIST gene may play a role in lead deposition in bones and calcium metabolism.