This meta-analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis.
Because PNPLA3rs738409, GCKR rs780094 and TM6SF2 rs58542926 variants are known to confer susceptibility to NAFLD, we assessed the influence of MBOAT7 rs641738 on hepatic steatosis, and serum levels of CK-18 fragment (a biomarker of hepatocellular injury and apoptosis for NAFLD) after adjusting the effects of PNPLA3, GCKR and TM6SF2 polymorphisms.
A recent finding that a nonsynonymous polymorphism in the PNPLA3 gene predicts the extent of steatosis in NAFLD has been replicated in at least eight studies, with several studies also demonstrating an association with fibrosis.
Using a 443 patient training set, protein biomarker discovery was performed using the highly multiplexed SOMAscan<sup>®</sup> proteomic assay, a set of 19 clinical variables, and the steatosis predisposing PNPLA3rs738409 single nucleotide polymorphism genotype status.
Since DAG (FA18:1) has been implicated in hepatic insulin resistance, the unaltered proportion of DAG (FA18:1) in I148MPNPLA3 carriers with fatty liver may explain the normal insulin sensitivity in these subjects.
Although African Americans are less susceptible to fatty liver than European Americans, PNPLA3 appears to be a risk locus for hepatic steatosis in diabetic African Americans.
IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis.
Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver.
The presence of the minor PNPLA3p.I148M risk allele increased the risk of developing NAFLD (OR = 3.29, P < 0.001) and was associated with higher steatosis, fibrosis, and serum CK18-M30 levels (all P < 0.05).
This study aimed to confirm the association of the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant with non-alcoholic fatty liver disease (NAFLD) and the degree of steatosis, as well as the additive effect of body mass index (BMI) or the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M and TM6SF2 E167K variants in NAFLD.
Reduction of Caloric Intake Might Override the Prosteatotic Effects of the PNPLA3p.I148M and TM6SF2 p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study.
In multivariable analysis, HIV infection was associated with a lower prevalence of fatty liver (odds ratio (OR)=0.44, P=0.002), whereas a higher prevalence of fatty liver was seen in participants with PNPLA3 (rs738409) non-CC genotype (OR=2.06, P=0.005), more abdominal visceral adipose tissue (OR=1.08 per 10 cm(2), P<0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) ≥4.9 (OR=2.50, P=0.001).
The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1).
We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.
However, PNPLA3rs2294918rs2294918" genes_norm="80339">E434K decreased PNPLA3 expression, lessening the effect of the I148M variant on the predisposition to steatosis and liver damage.
Interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) gene polymorphisms are associated with hepatitis C virus (HCV) clearance and fatty liver, respectively.