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

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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.

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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

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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).

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Authors and Affiliations

  1. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, 70 El Venizelou Ave, 17671, Athens, Greece

    I. P. Kalafati, M. Dimitriou, D. Borsa & G. V. Dedoussis

  2. First Department of Propaedeutic Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, 11527, Athens, Greece

    J. Vlachogiannakos, A. Kokkinos & S. D. Ladas

  3. Radiology Department, Laiko General Hospital, 11527, Athens, Greece

    K. Revenas

Authors
  1. I. P. Kalafati
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  2. M. Dimitriou
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Correspondence to I. P. Kalafati.

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Kalafati, I.P., Dimitriou, M., Borsa, D. et al. Fish intake interacts with TM6SF2 gene variant to affect NAFLD risk: results of a case–control study. Eur J Nutr 58, 1463–1473 (2019). https://doi.org/10.1007/s00394-018-1675-4

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  • DOI: https://doi.org/10.1007/s00394-018-1675-4

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