Non-alcoholic fatty liver disease and metabolic syndrome in adolescents: Pathogenetic role of genetic background and intrauterine environment

Figures & data

Table I. Diagnostic criteria for MetS in children and adolescents.

Parameters	Cook et al. 2003	de Ferranti et al. 2004
Waist circumference	≥90th percentile (age- and sex-specific)	>75th percentile (age- and sex-specific)
Triglycerides	≥110 mg/dL	≥100 mg/dL
HDL cholesterol	≤40 mg/dL	<50 mg/dL (<45 in boys aged 15–19 years)
Blood pressure	≥90th percentile (age-, sex-, and height-specific)	≥90th percentile (age-, sex-, and height-specific)
Fasting glucose	≥110 mg/dL	≥110 mg/dL

Table II. IDF definition for paediatric MetS.

Age	MetS
<6 years	No diagnosis
≥6 to <10 years	Obesity^a
	Additional measurements are suggested if there is a family history of MetS, type 2 diabetes, dyslipidaemia, cardiovascular disease, hypertension, or obesity
≥10 to <16 years	Obesity^a
	Adult criteria for:
	Triglycerides ≥1.7 mmol/L
	HDL cholesterol <1.03 mmol/L
	Blood pressure ≥130 mmHg systolic or ≥85 mmHg diastolic
	Fasting plasma glucose levels ≥5.6 mmol/L
	Presence of type 2 diabetes
≥16 years	Central obesity^a with ethnicity-specific values^b
	Plus two of the following conditions:
	Triglycerides ≥1.7 mmol/L
	HDL cholesterol <1.03 mmol/L in males and <1.29 mmol/L in females
	Blood pressure ≥ 130 mmHg systolic or ≥85 mmHg diastolic
	Fasting plasma glucose levels ≥5.6 mmol/L

^aDefined as ≥90th percentile of waist circumference.

^bIf BMI is >30 kg/m², central obesity can be assumed and no measurement of waist circumference is required.

Figure 1. Schematic representation of pathogenetic mechanisms leading to NAFLD. Genetic predisposition and environmental factors (i.e. diet) are determinant in the early events leading to fatty liver, including insulin resistance and fatty liver accumulation. Gut-derived endotoxaemia contributes to the early onset of steatosis as well as to the progression to NASH concomitantly to the oxidative stress and adipocytokines. Cell and tissue-specific alterations that characterize NASH are determined by all these events during NAFLD pathogenesis.

Figure supplied by A. Alisi.

Table III. Gene polymorphisms found in NAFLD and their correlation with MetS.

Gene	Polymorphism	MetS	Ref.
TNF-alpha	−238 and −308, −1031, −863, −857, −308 and −238	−308 is associated with obesity, hypertension and insulin resistance	(86,87)
microsomal triglyceride transfer protein	−493G/T polymorphism	association with components of MetS	(88)
methylenetetrahydrofolate reductase	C677T and A1298C	no relevant association	–
adiponectin	45G/T and 276G/T	these and other polymorphisms correlate with traits of MetS	(89,90)
peroxisome proliferator-activated receptor gamma coactivator 1alpha,	rs2290602	the association is controversial	(91,92)
peroxisome proliferator-activated receptor alpha	PPARalpha-L162V	association with components of MetS	(93)
leptin receptor	G3057A	other leptin receptor polymorphisms associate with high risk of insulin resistance and MetS	(94)
hepatic lipase	−514C/T	associated to MetS	(95,96)
haemochromatosis (HFE)	C282Y/H63D	no relevant association	–
apolipoprotein A5	APOA5, c.553G/T	association with components of MetS	(97)
adiponutrin/patatin-like phospholipase domain-containing-3	rs738409	adiponutrin polymorphisms associated with obesity but data on MetS are still not available	(98)

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