Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study

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• 作者：Emmi Suomela¹ ; ^{emkasu@utu.fi" class="auth_mail" title="E-mail the corresponding author} ; Mervi Oikonen¹ ; Niina Pitkä ; nen¹ ; Ari Ahola-Olli¹ ; Johanna Virtanen² ; Riitta Parkkola² ; Eero Jokinen³ ; Tomi Laitinen⁴ ; Nina Hutri-Kä ; hö ; nen⁵ ; Mika Kä ; hö ; nen⁶ ; Terho Lehtimä ; ki⁷ ; Leena Taittonen⁸ ; Pä ; ivi Tossavainen⁹ ; Antti Jula¹⁰ ; Britt-Marie Loo¹⁰ ; Vera Mikkilä ; ¹ ; ¹¹ ; Risto Telama¹² ; Jorma S.A. Viikari¹³ ; Markus Juonala¹³ ; Olli T. Raitakari¹ ; ¹⁴
• 关键词：SNP ; single nucleotide polymorphism ; PNPLA3 ; patatin-like phospholipase domain-containing 3 ; BMI ; body mass index ; CRP ; C-reactive protein ; OR ; odds ratios
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：4
• 页码：784-790
• 全文大小：716 K

文摘

Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults.

Methods

Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3–18 years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver.

Results

Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio = 1.71, 95% confidence interval = 1.07–2.72), variant in PNPLA3 (1.63, 1.29–2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08–2.30), BMI (1.30, 1.07–1.59 per standard deviation) and insulin (1.25, 1.05–1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p = 0.002).

Conclusions

Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes.

Lay summary

The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3–18 years) risk variables with fatty liver assessed in adulthood at the age of 34–49 years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.