Independent and joint correlation of PNPLA3 I148M and TM6SF2 E167K variants with the risk of coronary heart disease in patients with non-alcoholic fatty liver disease

Jian-Ting Wu,Qun Liu,Shi-Ying Xuan,Shou-Sheng Liu,Xiang-Jun Xie,Yong-Ning Xin

doi:10.1186/s12944-020-01207-9

Jian-Ting Wu, Qun Liu + Show 4 more

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https://doi.org/10.1186/s12944-020-01207-9

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Abstract

BackgroundCHD is reported to be the primary cause of death in patients with NAFLD. Genetic susceptibility genes contribute to the developmental risk of NAFLD or CHD. Whether the genetic factors could affect the risk of CHD in NAFLD patients is not clear. The aim of this study was to investigate the association of PNPLA3 I148M and TM6SF2 E167K variants with the risk of CHD in NAFLD patients in Chinese Han population.Patients and methodsPNPLA3 I148M and TM6SF2 E167K variants were genotyped in a cohort of 189 patients with NAFLD and CHD, as well as 242 patients with NAFLD and 242 healthy controls by gene sequencing. Additionally, serum lipids profiles were determined by standard clinical laboratory methods.ResultsThe minor allele frequency of PNPLA3 I148M and TM6SF2 E167K were 0.39 and 0.06 in this cohort, respectively. The distributions of PNPLA3 I148M genotypes and alleles were significant different in NAFLD group vs controls and in NAFLD+CHD group vs NAFLD group (all P < 0.05). NAFLD patients who carry the CG + GG genotype suffered the relative lower risk of CHD than CC genotype carriers (OR = 0.6, 95%CI: 0.40–0.90, P = 0.01). In addition, PNPLA3 I148M and TM6SF2 E167K possess the joint correlation with the decreased risk of CHD in NAFLD patients with the increased number of risk alleles. Besides, PNPLA3 I148M and TM6SF2 E167K variants associated with the decreased serum lipid levels in overall series.ConclusionsThere was a joint protective correlation of PNPLA3 I148M and TM6SF2 E167K variants with the developmental risk of CHD in NAFLD patients. PNPLA3 I148M and TM6SF2 E167K variants might correlated with the decreased risk of CHD in NAFLD patients by associated with the reduced serum lipid levels.

Highlights

coronary heart disease (CHD) is reported to be the primary cause of death in patients with Non-alcoholic fatty liver disease (NAFLD)
PNPLA3 I148M and TM6SF2 E167K variants might correlated with the decreased risk of CHD in NAFLD patients by associated with the reduced serum lipid levels
There were significant difference of serum fasting plasma glucose (FPG) and high-density lipoprotein (HDL) levels in NAFLD+CHD patients compared to NAFLD patients or health controls, but no obviously difference was observed between NAFLD patients and health controls (P > 0.05)

Summary

Introduction

CHD is reported to be the primary cause of death in patients with NAFLD. Genetic susceptibility genes contribute to the developmental risk of NAFLD or CHD. Whether the genetic factors could affect the risk of CHD in NAFLD patients is not clear. The aim of this study was to investigate the association of PNPLA3 I148M and TM6SF2 E167K variants with the risk of CHD in NAFLD patients in Chinese Han population. Many studies had investigated the roles of PNPLA3 I148M and TM6SF2 E167K in different countries and ethnic, and the results proven that PNPLA3 I148M and TM6SF2 E167K variants were the risk factors for the development of NAFLD [10,11,12,13]. PNPLA3 I148M and TM6SF2 E167K variants were found to have additive effect on increasing the NAFLD risk in Chinese Han population [14, 15]. Pirola conducted a metaanalysis to investigate the role of TM6SF2 E167K in patients with NAFLD and CHD, and they found that TM6SF2 E167K may possess the dual and opposite role in protecting against CHD and increase the risk of NAFLD [16,17,18]

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