EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

Chun-Xiao Liu; Rui-Xing Yin; Xiao-Li Cao; Zong-Hu Shi; Feng Huang; Bi-Liu Wei; Guo-Xiong Deng; Peng-Fei Zheng; Yao-Zong Guan

doi:10.3389/fgene.2022.843661

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

Front Genet. 2022 Apr 26:13:843661. doi: 10.3389/fgene.2022.843661. eCollection 2022.

Authors

Chun-Xiao Liu¹, Rui-Xing Yin¹, Xiao-Li Cao², Zong-Hu Shi³, Feng Huang¹, Bi-Liu Wei¹, Guo-Xiong Deng¹, Peng-Fei Zheng¹, Yao-Zong Guan¹

Affiliations

¹ Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
² Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
³ Department of Prevention and Health Care, The Fourth Affiliated Hospital, Guangxi Medical University, Liuzhou, China.

Abstract

The associations among the EH domain-binding protein 1 (EHBP1), tubulin beta class I (TUBB), and WW domain-containing oxidoreductase (WWOX) single nucleotide polymorphisms (SNPs) and coronary artery disease (CAD) and ischemic stroke (IS) are not yet understood. This study aimed to detect the associations of these SNPs, gene-gene and gene-environment interactions and CAD and IS in the Guangxi Han population. A total of 1853 unrelated subjects were recruited into normal control (n = 638), CAD (n = 622), and IS (n = 593) groups. Related genotypes were determined by high-throughput sequencing. The genotypic and minor allelic frequencies of rs2278075 were different between the CAD and control groups, and those of rs2710642, rs3130685, and rs2278075 were also different between the IS and control groups. The rs2278075T allele, rs3130685-rs2222896-rs2278075, rs3130685-rs2222896-diabetes, rs3130685-rs2222896-drinking, and haplotype rs2710642A-rs10496099C-diabetes interactions were associated with increased risk, while G-T-G-C-G-A and G-T-T-T-G-T-drinking were associated with reduced risk of CAD. The rs2278075T and rs2710642G alleles, rs2710642G-rs10496099C haplotype, rs3130685-rs2278075-rs2222896, and rs2710642-rs2278075-hypertension interactions aggravated the association with IS, whereas the rs3130685T allele, rs2710642A-rs10496099C haplotype and the interactions of H1 (s2710642A-rs10496099C)-H2 (rs2710642G-rs10496099C)-drinking and I1 (A-C-G-C-A-A)-I3 (A-C-G-T-A-A)-I4 (A-C-G-T-G-A)-I5 (G-T-G-C-G-A) diminished the association with IS. Carrying WWOX rs2278075T was strongly associated with CAD or IS, while EHBP1 rs2710642 and TUBB rs3130685 might alter the association of IS by modifying the serum lipid profile. This study demonstrates that the EHBP1, TUBB, and WWOX SNPs, gene-gene and gene-environment interactions are associated with the risk of CAD and IS in the Guangxi Han population.

Keywords: EH domain-binding protein 1; WW domaincontaining oxidoreductase; coronary artery disease; ischemic stroke; single nucleotide polymorphism; tubulin beta class I.