Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD.
Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD.
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DOI：
10.14309/ajg.0000000000001072
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发表时间：
2021-05-01
期刊：
影响因子：
--
通讯作者：
Chalasani N
中科院分区：
文献类型：
--
作者：
Vilar-Gomez E;Pirola CJ;Sookoian S;Wilson LA;Belt P;Liang T;Liu W;Chalasani N
This study explored the relationship between PNPLA3 rs738409, nutrient intake, and liver histology severity in patients with nonalcoholic fatty liver disease (NAFLD). PNPLA3-rs738409 variant was genotyped in 452 non-Hispanic whites with histologically confirmed NAFLD who completed Food Frequency Questionnaire within 6 months of their liver biopsy. The fibrosis severity on liver histology was the outcome of interest. The distribution of PNPLA3 genotypes was CC: 28%, CG: 46% and GG: 25%. High carbohydrate (% of energy/day) intake was positively associated (Adjusted [Adj]. OR: 1.03, P<.01), whereas higher n-3 polyunsaturated fatty acids (n-3 PUFAs) (g/day) (Adj. OR: 0.17, P<.01), isoflavones (mg/day) (Adj. OR: 0.74, P=.049), methionine (mg/day) (Adj. OR: 0.32, P<.01), and choline (Adj. OR: 0.32, P<.01) intakes were inversely associated with increased risk of significant fibrosis (stage of fibrosis ≥2). By using an additive model of inheritance, our moderation analysis showed that PNPLA3 rs738409 significantly modulates the relationship between carbohydrate (%), n-3 PUFAs, isoflavones, methionine, and choline intakes and fibrosis severity in a dose-dependent, genotype manner. These dietary factors tended to have a larger and significant effect on fibrosis severity amongst rs738409 G-allele carriers. Associations between significant fibrosis and carbohydrates (Adj. OR: 1.04, P=.019), n-3 PUFAs (Adj. OR: 0.16, P<.01), isoflavones (Adj. OR: 0.65, P=.025), methionine (Adj. OR: 0.30, P<.01), and choline (Adj. OR: 0.29, P<.01) intakes remained significant only amongst rs738409 G-allele carriers. This gene-diet interaction study suggests that PNPLA3 rs738409 G-allele might modulate the effect of specific dietary nutrients on risk of fibrosis in patients with NAFLD.
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