Research Paper Volume 12, Issue 12 pp 11893—11913

Association of the NCAN-TM6SF2-CILP2-PBX4-SUGP1-MAU2 SNPs and gene-gene and gene-environment interactions with serum lipid levels

Guo-Xiong Deng1, , Rui-Xing Yin1,2,3, , Yao-Zong Guan1, , Chun-Xiao Liu1, , Peng-Fei Zheng1, , Bi-Liu Wei1, , Jin-Zhen Wu1, , Liu Miao4, ,

  • 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 Cardiology, Liuzhou People’s Hospital, Liuzhou 545006, Guangxi, People’s Republic of China

Received: January 5, 2020       Accepted: May 1, 2020       Published: June 22, 2020      

https://doi.org/10.18632/aging.103361
How to Cite

Copyright © 2020 Deng 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.

Abstract

This study investigated the association of the NCAN-TM6SF2-CILP2-PBX4-SUGP1-MAU2 SNPs and gene-gene and gene-environment interactions with serum lipid levels in the population of Southwest China. Genotyping of 12 SNPs (i.e., rs2238675, rs2228603, rs58542926, rs735273, rs16996148, rs968525, rs17216525, rs12610185, rs10401969, rs8102280, rs73001065 and rs150268548) was performed in 1248 hyperlipidemia patients and 1248 normal subjects. The allelic and genotypic frequencies of the detected SNPs differed substantially between the normal and hyperlipidemia groups (P < 0.05-0.001), and the association of the 12 SNPs and hyperlipidemia was also observed (P < 0.004-0.0001). Four haplotypes (i.e., NCAN C-C, CILP2 G-T, PBX4-SUGP1 G-C, and MAU2 C-A-G-T) and 5 gene-gene interaction haplotypes (i.e., rs2238675C-rs2228603C, rs16996148G-rs17216525T, rs12610185G-rs10401969C, rs73001065G-rs8102280A-rs150268548G-rs968525C and rs73001065C-rs8102280A-rs150268548G-rs96852)showed a protective effect, whereas four other haplotypes (i.e., TM6SF2 T-A, TM6SF2 C-A, MAU2 G-G-G-C and MAU2 C-G-A-T), as well as 4 gene-gene interaction haplotypes (i.e., rs58542926C-rs735273A, rs58542926T-rs735273A, rs73001065G-rs8102280G-rs150268548G-rs968525C, and rs73001065C-rs8102280G-rs150268548A-rs968525T), exhibited an inverse effect on hyperlipidemia (P < 0.05-0.0001). There were notable three-locus models comprising SNP-SNP, SNP-environment, and haplotype-haplotype interactions (P < 0.05-0.0001). The individuals with some genotypes and haplotypes reduced the prevalence of hyperlipidemia, whereas the individuals with some other genotypes and haplotypes augmented the prevalence of hyperlipidemia. The NCAN-TM6SF2-CILP2-PBX4-SUGP1-MAU2 SNPs and gene-gene and gene-environment interactions on hyperlipidemia were observed in the population of Southwest China.

Abbreviations

Apo: apolipoprotein; BMI: body mass index; CAD: coronary artery disease; CILP2: the cartilage intermediate layer protein 2 gene; CVDs: cardiovascular diseases; DNA: deoxyribonucleic acid; E: environment; G: gene; GWAS: genome-wide association studies; HDL-C: high-density lipoprotein cholesterol; HMGCR: 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; HTGC: hepatic triglyceride content; HWE: Hardy-Weinberg equilibrium; JNC-7: the Seventh Report of Joint National Committee; LD: linkage disequilibrium; LDL-C: low-density lipoprotein cholesterol; MAF: minor allele frequency; MAU2: the MAU2 sister chromatid cohesion factor gene; NAFLD: non-alcoholic fatty liver disease; NCAN: the neurocan gene; PBX4: the PBX homeobox 4 gene; siRNA: small interfering Ribonucleic Acid; SNP: single nucleotide polymorphism; SUGP1: the SURP and G-patch domain containing 1 gene; TC: total cholesterol; TG: triglyceride; TM6SF2: the transmembrane 6 superfamily member 2 gene.