PNPLA3 rs738409 G-allele modulates effect of nutrients on fibrosis risk in NAFLD

The interaction between genetic variation and dietary intake suggests that PNPLA3 rs738409 G-allele may modify the effect of certain dietary nutrients on the risk of significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), reports a study.

The investigators genotyped the PNPLA3-rs738409 variant in 452 non-Hispanic Whites with histologically confirmed NAFLD who completed the food frequency questionnaire within 6 months of their liver biopsy. The primary outcome was fibrosis severity on liver histology.

The distribution of PNPLA3 genotypes was 28 percent CC, 46 percent CG, and 25 percent GG. High-carbohydrate intake positively correlated (adjusted odds ratio [aOR], 1.03; p<0.01), while higher n-3 polyunsaturated fatty acids (n-3 PUFAs; aOR, 0.17; p<0.01), isoflavones (aOR, 0.74; p=0.049), methionine (aOR, 0.32; p<0.01), and choline (aOR, 0.32; p<0.01) intakes inversely correlated with a higher risk of significant fibrosis (stage ≥2).

In a moderation analysis that used an additive model of inheritance, PNPLA3 rs738409 significantly modulated the relationship between carbohydrate, n-3 PUFAs, total isoflavones, methionine, and choline intakes and fibrosis severity in a dose-dependent, genotype manner. These dietary factors appeared to have a greater and significant effect on fibrosis severity among rs738409 G-allele carriers.

Significant associations between significant fibrosis and carbohydrates (aOR, 1.04; p=0.019), n-3 PUFAs (aOR, 0.16; p<0.01), isoflavones (aOR, 0.65; p=0.025), methionine (aOR, 0.30; p<0.01), and total choline (aOR, 0.29; p<0.01) intakes persisted only among rs738409 G-allele carriers.