Genome-wide association studies have shown that a non-synonymous single nucleotide polymorphism characterized by a C-to-G change encoding an isoleucine-to-methionine substitution at amino acid position 148 in the human patatin-like phospholipase 3 (PNPLA3) gene was found to be associated with non-alcoholic fatty liver disease (NAFLD) and advanced liver damage. A hospital-based study was conducted to determine the distribution of PNPLA3 genotypes among patients clinically diagnosed and histologically confirmed with NAFLD and among normal controls. We also compared the allelic frequencies of PNPLA3 with different ethnic populations. More importantly, we evaluated the association between PNPLA3 genetic variation and risk of developing NAFLD among Filipinos. Real-time PCR was performed using the Taqman SNP genotyping assay for rs738409. Nucleotide sequencing was performed to confirm the PNPLA3 genotypes. Allelic frequencies among normal controls were 0.83 and 0.17 for the PNPLA3 C and PNPLA3 G alleles, respectively. Calculated frequencies in Hardy Weinberg Equilibrium were 72% for PNPLA3 C/C, 22% for PNPLA3 C/G, and 6% for PNPLA3 G/G genotype. There is a significant difference in the distribution of PNPLA3 genotypes between normal controls and NAFLD patients (p = 0.0172). However, there was no significant association found between PNPLA3 genotypes and risk of developing NAFLD after controlling for possible confounding effects (p = 0.0574). Allelic frequencies of PNPLA3 among Filipinos were statistically different from Hispanics, Japanese, and Han Chinese. In conclusion, genetic variation in PNPLA3 rs738409 C>G seems to be associated with NAFLD among Filipinos. Further studies are needed to replicate our observations in an independent larger population.
Keywords: Filipino; Genetic variation; I148M; non-alcoholic fatty liver disease; patatin-like phospholipase 3 gene; rs738409 C>G.