OBJECTIVETo study the relationship between the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hereditary susceptibility to non-alcoholic fatty liver disease (NAFLD) by detecting single nucleotide polymorphisms (SNPs).

METHODSPeripheral blood DNA from 315 patients diagnosed with NAFLD (including the spectrum of simple steatosis (SS) and non-alcoholic steatosis (NASH)) and 336 control subjects was used to determine the PNPLA3 genotype by polymerase chain reaction (PCR) and direct sequencing. The relationship of SNPs and NAFLD-related markers of liver function were assessed by correlation analysis.

RESULTSThe SNP rs738409 was identified in more of the NAFLD patients (allele variant frequencies: NAFLD, 65.40%; NASH: 71.87%; SS, 56.47%) than in the controls (33.18%). Case-control analysis revealed that carriers of the 148GG genotype were at 3.81-fold (95% CI: 3.03 ~ 4.79) higher risk of developing NAFLD and at 1.97-fold (95% CI: 1.41 ~ 2.75) higher risk of progressing from SS to NASH, compared with non-carriers. rs738409 was also found to be associated with serum levels of alanine aminotransferase (ALT) and y-glutamyltransferase (y-GT) (both P less than 0.05). Carriers of the 148GG genotype had significantly higher body mass index, ALT, and fasting insulin than carriers of the 148CC genotype (all P less than 0.05), and significantly higher level of serum HDL than carriers of either the 148CC genotype or the 148GC genotype (both P less than 0.05).

CONCLUSIONPolymorphisms in the PNPLA3 gene may play an important role in mediating susceptibility to developing NAFLD in the Chinese population. The rs738409 polymorphism, in particular, is related to development and progression of NAFLD and may play a role in the contribution of PNPLA3 to NAFLD pathogenesis.