Table 1.
Number of the studies evaluating the association between PNPLA3 I148M and liver damage
| Study | Population | N | Key findings |
|---|---|---|---|
| Romeo et al47 | American-European and African origin, Hispanics | 2111 | I148M was associated with increase in liver fat in all participants and increased ALT and AST in Hispanics. Genome-wide association study HS was measured by 1H-MRS |
| Valenti et al53 | Italy and UK | 432/321 | Patients with NAFLD I148M were associated with the severity of steatosis and fibrosis and presence of NASH. Hepatic steatosis was diagnosed with LB |
| Hotta et al50 | Japanese NAFLD/Controls | 253/578 | I148M was susceptible to NAFLD. Associated with ALT, AST, ferritin and histological fibrosis stage |
| Tian et al61 | Mestizo subjects | The rs7,38,409 in PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis | |
| Stickel et al63 | German cohort | 1043 | The rs7,38,409 in PNPLA3 is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians |
| Rotman et al51 | USA NAFLD | 894 | Association of I148M with steatosis, ALT and fibrosis. Liver biopsy proved NAFLD |
| Sookoian and Pirola49 | Meta-analysis | 16 studies | rs7,38,409 G allele had strong influence on liver fat accumulation plus susceptibility of more aggressive disease. Increase in serum ALT |
| Valenti et al69 | Italians | 819 | rs7,38,409 influenced steatosis in CHC. Independently associated with cirrhosis and HCC |
| Trepo et al70 | Caucasian CHC |
537 | PNPLA3 rs7,38,409 C>G polymorphism favored steatosis and fibrosis in CHC |
| Zain et al54 | Chinese, Indian and Malay | 144/198 | The G allele was positively correlated with susceptibility to NASH, NASH severity and presence of fibrosis |
| Burza et al89 | Swedish obese subjects cohort | 4047 | Association of the PNPLA3 I148M and HCC in obese individuals who had not undergone bariatric surgery |
| Vigano et al78 | CHB patients | 235 | In CHB patients the PNPLA3 I148M influences susceptibility to steatosis and, in particular, when associated with severe overweight and alcohol intake, severe steatosis |
| Liu et al88 | European Caucasians with NAFLD-related HCC | 100 | PNPLA3 I148M is associated with greater risk of progressive steatohepatitis and fibrosis but also of HCC |
| Trepo et al87 | Meta-analysis | 2503 | rs7,38,409 was strongly associated with HCC in cirrhotic patients, particularly pronounced in ALD than in CHC etiology |
| Singal et al55 | Europeans, Asians/NAFLD, ALD, CHC, CHB | 9915 | PNPLA3 associates to advance fibrosis, NAFLD and ALD |
| De Nicola et al72 | Europeans CHC | 247 | Interaction between homozygosity for the PNPLA3 I148M variant in determining fibrosis progression |
| Brouwer et al79 | CHB patients | 531 | PNPLA3 was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions |
| Stattermayer et al81 | Wilson disease | 98 | The PNPLA3 I148M predisposes to increased steatosis development in patients with Wilson disease |
| Krawczyk et al90 | Meta-analysis | 5100 | The I148M PNPLA3 genetic variant is associated with increased risk of developing HCC in NAFLD patients |
| Luukkonen et al59 | Finnish cohort | 125 | Metabolically harmful saturated, ceramide-enriched liver lipidome in “Metabolic NAFLD” but not in “PNPLA3 NAFLD” |
| Mancina et al82 | IBD (Italy) | 158 | PNPLA3 I148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage |
| Atkinson et al66 | UK/Irish | 1188 | Carriers of the genetic variant of PNPLA3 are more at risk of developing severe alcoholic hepatitis and have less survival even after stopping drinking |
Abbreviations: ALD, alcoholic fatty liver disease; ALT, alanine transaminase; AST, aspartate transaminase; CHB, chronic hepatitis B; CHC, chronic hepatitis C; HCC, hepatocellular carcinoma; HS, hepatic steatosis; IBD, inflammatory bowel disease; LB, liver biopsy; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; T2DM type 2 diabetes mellitus.