Differential Effects of ABCG5/G8 Gene Region Variants on Lipid Profile, Blood Pressure Status, and Gallstone Disease History in Taiwan

Genes (Basel). 2023 Mar 20;14(3):754. doi: 10.3390/genes14030754.

Abstract

ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between ABCG5/G8 gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 Taiwan Biobank participants with whole-genome sequencing data and 117,679 participants with Axiom Genome-Wide CHB Array data were enrolled for analysis. Using genotype-phenotype and stepwise linear regression analyses, we found independent associations of four Asian-specific ABCG5 variants, rs119480069, rs199984328, rs560839317, and rs748096191, with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels (all p ≤ 0.0002). Four other variants, which were in nearly complete linkage disequilibrium, exhibited genome-wide significant associations with gallstone disease history, and the ABCG8 rs11887534 variant showed a trend of superiority for gallstone disease history in a nested logistic regression model (p = 0.074). Through regional association analysis of various other cardiometabolic traits, two variants of the PLEKHH2, approximately 50 kb from the ABCG5/G8 region, exhibited significant associations with blood pressure status (p < 10-6). In conclusion, differential effects of ABCG5/G8 region variants were noted for lipid profile, blood pressure status, and gallstone disease history in Taiwan. These results indicate the crucial role of individualized assessment of ABCG5/G8 variants for different cardiometabolic phenotypes.

Keywords: ABCG5; ABCG8; differential effect; gallstone disease; genetic variants; lipid profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 8 / genetics
  • Blood Pressure / genetics
  • Cardiovascular Diseases*
  • Cholesterol
  • Gallstones* / genetics
  • Humans
  • Lipoproteins / genetics
  • Taiwan

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • Lipoproteins
  • Cholesterol
  • ABCG5 protein, human

Grants and funding

This study was supported by grants from Buddhist Tzu Chi Medical Foundation (TCMF-EP 111-02) and Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-112-02) to Y.-L.K.; Buddhist Tzu Chi Medical Foundation (TCMF-A 112-02) and Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-112-31) to K.-H.Y.; and Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-109-RT-1) to H.-H.C.