European Journal of Nutrition

, Volume 58, Issue 4, pp 1463–1473 | Cite as

Fish intake interacts with TM6SF2 gene variant to affect NAFLD risk: results of a case–control study

  • I. P. KalafatiEmail author
  • M. Dimitriou
  • D. Borsa
  • J. Vlachogiannakos
  • K. Revenas
  • A. Kokkinos
  • S. D. Ladas
  • G. V. Dedoussis
Original Contribution



Non-alcoholic fatty liver disease (NAFLD) is a complex disease, resulting from a variety of genetic and environmental factors. The aim of this case–control study was to evaluate the effect of selected genetic polymorphisms, nutrition aspects and their interaction on the risk of NAFLD.


The sample consisted of 134 patients with NAFLD and 217 controls. Disease was diagnosed by liver ultrasound and volunteers were clinically and nutritionally assessed. Food groups were extracted from a 172 food-item FFQ questionnaire. Three genetic polymorphisms were assessed: PNPLA3 rs738409, TM6SF2 rs58542926 and GCKR rs780094.


We replicated the effect of previously reported risk factors for NAFLD, such as elevated liver enzymes, obesity and metabolic syndrome. Food groups rich in simple sugars, fat and especially saturated fat were positively associated with NAFLD risk, whereas food groups rich in polyunsaturated fatty acids were reversely associated with the possibility of developing the disease (p < 0.05). Only the PNPLA3 genetic variant was statistically significantly associated with the disease (padditive = 0.015). However, it was found that a one-portion increase in fish intake increased the risk of NAFLD in carriers of the risk allele of TM6SF2 rs58542926 polymorphism compared to non-carriers, after adjusting for age, gender, energy intake, pack-years, PAL, TM6SF2 genotype and fish consumption (ORdominant = 1.503, 95% CI 1.094–2.064).


Fish intake exerts an additive effect on NAFLD risk for carriers of the TM6SF2 polymorphism. This novel finding provides further rationale on the need for personalized nutritional advice, based on the genetic background of NAFLD patients.


NAFLD Gene–diet interactions Fatty liver Genes Nutrition 





Alkaline phosphatase


Alanine transaminase


Athens physical activity questionnaire


Aspartate transaminase


Body mass index


C-reactive protein


Cardiovascular disease


Diastolic blood pressure






Fasting glucose


Fasting insulin


Gastroesophageal reflux disease


Genetic risk score


Glycated haemoglobin


High-density lipoprotein


Homeostatic model assessment


Impaired fasting glucose


Low-density lipoprotein


Metabolic syndrome


Monounsaturated fatty acids


Non-alcoholic fatty liver disease


Non-alcoholic steatohepatitis


NAFLD fibrosis score




Polyunsaturated fatty acids


Systolic blood pressure


Single nucleotide polymorphisms


Type 2 diabetes mellitus


Total cholesterol




White blood cells





This study was funded by the project “Obesity and metabolic syndrome: dietary intervention with Greek raisins in NAFLD/NASH. Investigation of molecular mechanisms” reviewed and approved by the Greek Secretariat for Research and Technology (Cooperation 890/2009).

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest relevant to this article were reported.

Supplementary material

394_2018_1675_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 22 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • I. P. Kalafati
    • 1
    Email author
  • M. Dimitriou
    • 1
  • D. Borsa
    • 1
  • J. Vlachogiannakos
    • 2
  • K. Revenas
    • 3
  • A. Kokkinos
    • 2
  • S. D. Ladas
    • 2
  • G. V. Dedoussis
    • 1
  1. 1.Department of Nutrition and Dietetics, School of Health Science and EducationHarokopio University of AthensAthensGreece
  2. 2.First Department of Propaedeutic Medicine, School of MedicineNational and Kapodistrian University of Athens, Laiko General HospitalAthensGreece
  3. 3.Radiology DepartmentLaiko General HospitalAthensGreece

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