Genetic variant I148M in PNPLA3 is associated with the ultrasonography-determined steatosis degree in a Chinese population

Background: Nonalcoholic fatty liver disease (NAFLD) is an escalating medical problem worldwide. A nonsynonymous single nucleotide polymorphism rs738409 (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) predisposes susceptibility to NAFLD; however, its association with steatosis grade is inconsistent in the literature. In particular, there was no significant association found between I148M and steatosis grade in two East Asian-based studies. In this study we aim to investigate whether I148M is associated with the ultrasonography-determined steatosis degree in Chinese adults.Methods: 203 NAFLD cases and 202 matched controls were recruited. Cases were classified into mild, moderate and severe fatty liver by ultrasonography. Association between I148M and the ultrasonography-determined steatosis degree as well as other clinical parameters was evaluated.Results: The I148M variant was associated with the ultrasonography-determined steatosis degree with the M allele frequencies being 0.32, 0.54, and 0.87 in mild (n=105), moderate (n=83), and severe (n=15) cases, respectively (P-value = 7.6×10^-8). We also confirmed the interaction between I148M variation and body mass index towards elevated plasma alanine aminotransferase levels in cases (P-value = 4.4×10^-4).Conclusion: The PNPLA3 I148M variant is associated with the ultrasonography-determined steatosis degree in Chinese population.