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

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

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

NAFLD Gene–diet interactions Fatty liver Genes Nutrition 

Abbreviations

Alb

Albumin

ALP

Alkaline phosphatase

ALT

Alanine transaminase

APAQ

Athens physical activity questionnaire

AST

Aspartate transaminase

BMI

Body mass index

CRP

C-reactive protein

CVD

Cardiovascular disease

DBP

Diastolic blood pressure

Fe

Iron

Fer

Ferritin

FGlu

Fasting glucose

FIns

Fasting insulin

GERD

Gastroesophageal reflux disease

GRS

Genetic risk score

HbA1c

Glycated haemoglobin

HDL

High-density lipoprotein

HOMA-IR

Homeostatic model assessment

IFG

Impaired fasting glucose

LDL

Low-density lipoprotein

MetS

Metabolic syndrome

MUFAs

Monounsaturated fatty acids

NAFLD

Non-alcoholic fatty liver disease

NASH

Non-alcoholic steatohepatitis

NFS

NAFLD fibrosis score

PLT

Platelets

PUFAs

Polyunsaturated fatty acids

SBP

Systolic blood pressure

SNPs

Single nucleotide polymorphisms

T2DM

Type 2 diabetes mellitus

TC

Total cholesterol

TG

Triglycerides

WBC

White blood cells

γ-GT

Gamma-glutamyltransferase

Notes

Acknowledgements

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
  • 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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