The I148M variant of PNPLA3 reduces the response to docosahexaenoic acid in children with non-alcoholic fatty liver disease.
The aim of this secondary analysis of a randomized controlled trial was to test whether the I148M variant of Patatin-like phospholipase domain-containing protein-3 (PNPLA3) is associated with the response to docosahexaenoic acid (DHA) in children with non-alcoholic fatty liver disease (NAFLD). Sixty children with NAFLD were randomized in equal numbers to DHA 250 mg/day, DHA 500 mg/day or placebo. Coherently with the primary analysis, the probability of more severe steatosis after 24 months of DHA supplementation was 50% lower [95% confidence interval (CI) -59% to -42%)] in the combined DHA 250 and 500 mg/day groups versus placebo. The present secondary analysis revealed an independent effect of PNPLA3 status on the response to DHA. In fact, the probability of more severe steatosis was higher (37%, 95% CI 26-48%) for the PNPLA3 M/M versus I/M genotype and lower (-12%, 95% CI -21% to -3%) for the I/I versus I/M genotype (Somers' D for repeated measures). We conclude that the 148M allele of PNPLA3 is associated with lower response, and the 148I allele with greater response, to DHA supplementation in children with NAFLD.
1 Hepatometabolic Unit, Bambino Gesù Children's Hospital , Roma, Italy .
Valerio
V
Nobili
Giorgio
G
Bedogni
Benedetta
B
Donati
Anna
A
Alisi
Luca
L
Valenti
D002648:Child; D002675:Child, Preschool; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006801:Humans; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D065626:Non-alcoholic Fatty Liver Disease; D016896:Treatment Outcome; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D004281:Docosahexaenoic Acids; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent