Key result
The PNPLA3 variant was associated with increased steatosis (P=0.004) and fibrosis (P=0.042), whereas TM6SF2 was linked to steatosis (P=0.038) and MBOAT7 to fibrosis (P=0.021).
Why the study?
Do the PNPLA3, TM6SF2, and MBOAT7 genetic variants modulate steatosis and fibrosis severity in patients with NAFLD?
Cross-Sectional (n=515)
Yes
Do the PNPLA3, TM6SF2, and MBOAT7 genetic variants modulate steatosis and fibrosis severity in patients with NAFLD?
The PNPLA3 variant increases risk for both steatosis and fibrosis, whereas TM6SF2 predominantly modulates hepatic fat accumulation and MBOAT7 is linked to fibrosis in NAFLD patients.
Should not yet change NAFLD management; leaves open whether genotyping refines risk prediction or therapy selection.
The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16-88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants. Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P < 0.05). The PNPLA3 genotype was associated with steatosis grades S2-S3 (P < 0.001) and fibrosis stages F2-F4 (P < 0.001). The TM6SF2 genotype was associated with steatosis (P = 0.003) but not with fibrosis (P > 0.05). The MBOAT7 variant was solely associated with increased fibrosis (P = 0.046). In the multivariate model, variants PNPLA3 (P = 0.004) and TM6SF2 (P = 0.038) were associated with steatosis. Fibrosis stages were affected by the PNPLA3 (P = 0.042) and MBOAT7 (P = 0.021) but not by the TM6SF2 polymorphism (P > 0.05). The PNPLA3, TM6SF2, and MBOAT7 variants are associated with increased liver injury. The TM6SF2 variant seems to modulate predominantly hepatic fat accumulation, whereas the MBOAT7 polymorphism is linked to fibrosis. The PNPLA3 polymorphism confers risk of both increased steatosis and fibrosis.
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Krawczyk et al. (2016) conducted a cross-sectional in Nonalcoholic fatty liver disease (NAFLD) (n=515). PNPLA3, TM6SF2, and MBOAT7 genetic variants vs. Non-carriers was evaluated on Steatosis and fibrosis severity. The PNPLA3 variant was associated with increased steatosis (P=0.004) and fibrosis (P=0.042), whereas TM6SF2 was linked to steatosis (P=0.038) and MBOAT7 to fibrosis (P=0.021).
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