The A/A genotype at <i>PNPLA3</i> rs139051 exerts an up-regulatory effect on serum phospholipids of LPCs and LPCOs, which are associated with low-grade lobular inflammation of NAFLD.
We found that rs139051 did not independently affect the NAFLD risk, whilst rs738409 did not significantly modulate <i>PNPLA3</i> transcription but was associated with NAFLD risk.
In the multivariate logistic regression analysis, the rs738409 GG or GC, and rs139051 TT genotypes were found to be associated with increased risk of NAFLD, and a significant trend of increased risk with increasing numbers of risk genotype was observed in the cumulative effect analysis of these single nucleotide polymorphisms.