Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study.

OBJECTIVES: PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase (ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. METHODS: Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. RESULTS: Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after 2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up (P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. CONCLUSION: PNPLA3 148M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children.