Research Paper Volume 13, Issue 4 pp 5906—5927

Associations between TUBB-WWOX SNPs, their haplotypes, gene-gene, and gene-environment interactions and dyslipidemia

Chun-Xiao Liu1, , Rui-Xing Yin1,2,3, , Zong-Hu Shi4, , Peng-Fei Zheng1, , Guo-Xiong Deng1, , Yao-Zong Guan1, , Bi-Liu Wei1, ,

  • 1 Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China
  • 2 Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Disease Control and Prevention, Nanning 530021, Guangxi, People’s Republic of China
  • 3 Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning 530021, Guangxi, People’s Republic of China
  • 4 Department of Prevention and Health Care, The Fourth Affiliated Hospital, Guangxi Medical University, Liuzhou 545005, Guangxi, People’s Republic of China

Received: September 4, 2020       Accepted: December 29, 2020       Published: February 17, 2021
How to Cite

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


In this study, we investigated associations between single nucleotide polymorphisms (SNPs) in the tubulin beta class I (TUBB) and WW domain-containing oxidoreductase (WWOX) genes, gene-gene interactions, and gene-environment interactions and dyslipidemia in the Chinese Maonan ethnic group. Four SNPs (rs3132584, rs3130685, rs2222896, and rs2548861) were genotyped in unrelated subjects with normal lipid levels (864) or dyslipidemia (1129). While 5.0% of Maonan subjects carried the rs3132584TT genotype, none of the Chinese Han in Beijing subjects did. Allele and genotype frequencies differed between the normal and dyslipidemia groups for three SNPs (rs3132584, rs3130685, and rs2222896). rs2222896G allele carriers in the normal group had higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol levels. The rs3132584GG, rs3130685CC+TT, and rs2222896GG genotypes as well as the rs2222896G-rs2548861G and rs2222896G-rs2548861T haplotypes were associated with an elevated risk of dyslipidemia; the rs2222896A-rs2548861T and rs2222896A-rs2548861G haplotypes were associated with a reduced risk of dyslipidemia. Among the thirteen TUBB-WWOX interaction types identified, rs3132584T-rs3130685T-rs2222896G-rs2548861T increased the risk of dyslipidemia 1.371-fold. Fourteen two- to four-locus optimal interactive models for SNP-SNP, haplotype-haplotype, gene-gene, and gene-environment interactions exhibited synergistic or contrasting effects on dyslipidemia. Finally, the interaction between rs3132584 and rs2222896 increased the risk of dyslipidemia 2.548-fold and predicted hypertension.


Apo: apolipoprotein; Bal. Acc.: balanced accuracy; BMI: body mass index; CAD: coronary arteriosclerotic diseases; CHB: Chinese Han Beijing; CI: confidence interval; CV: cross-validation; DBP: diastolic blood pressure; GMDR: generalized multifactor dimensionality reduction; GWAS: genome-wide association study; HDL-C: high-density lipoprotein cholesterol; HWE: Hardy Weinberg Equilibrium; LD: linkage disequilibrium; LDL-C: low-density lipoprotein cholesterol; LFT: lowest frequency threshold; MAF: minor allele frequency; OR: odds ratio; PP: pulse pressure; FBS: fasting blood-glucose; RPKM: reads per kilobase per million mapped reads; SBP: systolic blood pressure; SNP: single nucleotide polymorphism; TC: total cholesterol; TG: triglyceride; TUBB: tubulin beta class I gene; WWOX: WW domain-containing oxidoreductase gene.