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. 2022 Jan 26;19(3):1352.
doi: 10.3390/ijerph19031352.

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

Chen-Cheng Yang  1   2   3 , Chia-Yen Dai  3 , Kuei-Hau Luo  1 , Kuo-Wei Lee  4 , Cheng-Hang Wu  5 , Chih-Hsing Hung  6 , Hung-Yi Chuang  3   7 , Chao-Hung Kuo  8
Affiliations

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

Chen-Cheng Yang et al. Int J Environ Res Public Health. .

Abstract

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.

Keywords: Taiwan biobank; genome-wide association study; high-density lipoprotein cholesterol (HDL-C); lead (Pb); single nucleotide polymorphism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The Manhattan plots of the genome-wide association study of HDL-C in Pb-exposed workers. Two SNPs were found—rs150813626 (single-nucleotide variation in the TWIST2 gene on chromosome 2), and rs1983079 (unclear SNP on chromosome 3).
Figure 2
Figure 2
(A). The interaction plot for the regression of the association between HDL-C and blood Pb level according to rs150813626 single nucleotide polymorphisms, GG, AG, and AA carriers. (B). The interaction plot for the regression of the association between HDL-C and blood Pb level according to rs1983079 single nucleotide polymorphisms, AA, AG, and GG carriers.
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