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Background  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.    Patients and methods   PNPLA3  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.    Results  The 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.    Conclusions  There 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.

lipids in health and disease

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