Effect of genetic and environmental influences on hepatic steatosis: A classical twin study based on computed tomography

Background and aims: Non-alcoholic fatty liver disease (NAFLD) increases cardiovascular morbidity and mortality, and carries poor long-term hepatic prognosis. Data about the role of genetic and environmental factors in the hepatic lipid accumulation are limited. The aim of the study was to evaluate the genetic and environmental impact on the hepatic lipid accumulation within a cohort of adult twin pairs. Patients and methods: We investigated 182 twin subjects [monozygotic (MZ, n = 114) and dizygotic (DZ, n = 68) same-gender twins (age 56.0 +/- 9.6 years; BMI 27.5 +/- 5.0 kg/m2; females 65.9%)] who underwent computed tomography (CT) with a 256-slice scanner. Using non enhanced CT-images, we calculated the average value of hepatic attenuation [expressed in Hounsfield unit (HU)] suggesting hepatic lipid content. Crude data were adjusted to age, sex, BMI and HbA1c values. Intra-pair correlations were established, and structural equation models were used for quantifying the contribution of additive genetic (A), common environmental (C) and unique environmental (E) components to the investigated phenotype. Results: The study cohort represented a moderately overweight, middle-aged Caucasian population. There was no significant difference between MZ and DZ twin subjects regarding hepatic CT-attenuation (57.9 +/- 12.6 HU and 59.3 +/- 11.7 HU, respectively; p = 0.747). Age, sex, BMI and HbA1c adjusted co-twin correlations between the siblings showed that MZ twins have stronger correlations of HU values than DZ twins (rMZ = 0.592, p < 0.001; rDZ = 0.047, p = 0.690, respectively). Using the structural equation model, a moderate additive genetic dependence (A: 38%, 95% CI 15-58%) and a greater unique environmental influence (E: 62%, 95% CI 42-85%) was found. Common environmental influence was not identified (C: 0%). Conclusion: The results of our classical CT-based twin study revealed moderate genetic and greater environmental influences on the phenotypic appearance of hepatic steatosis, commonly referred to as NAFLD. Favorable changes of modifiable environmental factors are of great importance in preventing or treating NAFLD.