The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis

Analysis of genotyping for predicting liver injury marker, procollagen III in persons at risk of non‐alcoholic fatty liver disease

“…We confirm that the PNPLA3 variant is significantly more prevalent in diagnosed, secondary care NAFLD patients, as previously reported in several populations and established as a risk factor for disease in meta‐analyses . Here, we additionally report increased prevalence of GCKR and TM6SF2 variants in biopsy‐proven NAFLD patients (Table ).…”

“…Three separate single nucleotide polymorphism functional variants, shown to confer increased susceptibility to hepatic triglyceride accumulations and fibrogenesis, have been robustly validated in large independent cohorts and supporting evidence provided by mechanistic studies. The rs738409 (C>G) variant in adiponutrin (PNPLA3) has consistently been demonstrated to correlate with increased severity of NAFLD . An association has also been established between the rs1260326 (C>T) variant within the glucokinase regulator (GCKR) and steatosis and fibrosis in NAFLD .…”

PNPLA3 gene in liver diseases

“…Other authors reported similar results and further highlighted the fact that rs738409 [G] was not merely associated with steatosis but also with severe liver damage throughout the NAFLD spectrum [12][13][14]. These findings have been summarized in several meta-analyses [15][16][17][18][19] (Table 1). Since the physiopathology of NAFLD is tightly related to the metabolic syndrome, a link between rs738409[G] and the parameters that define the metabolic syndrome was a likely hypothesis.…”

The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP)

“…Our group availed of non‐invasive assessment of liver fibrosis by transient elastography, demonstrating that the PNPLA3 variant increases liver stiffness and represents a risk factor for developing cirrhosis (OR = 1.56) in 899 patients with various CLDs . This finding is supported by a recent meta‐analysis reporting that the [M] allele results in an elevated cirrhosis risk as compared to the [I] allele (OR = 1.86) . As demonstrated in Pnpla3 p.148M knock‐in mice, the mutation leads to the accumulation of PNPLA3 on lipid droplets and an increase in triglyceride concentrations in liver in the presence of a dietary overload .…”