A Promoter Polymorphism in the Liver-specific Fatty Acid Transport Protein 5 is Associated with Features of the Metabolic Syndrome and Steatosis

A. Auinger; L. Valenti; M. Pfeuffer; U. Helwig; J. Herrmann; A. L. Fracanzani; P. Dongiovanni; S. Fargion; J. Schrezenmeir; D. Rubin

doi:10.1055/s-0030-1267186

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2010; 42(12): 854-859
DOI: 10.1055/s-0030-1267186

Original Basic

A Promoter Polymorphism in the Liver-specific Fatty Acid Transport Protein 5 is Associated with Features of the Metabolic Syndrome and Steatosis

A. Auinger¹ ^, ² , L. Valenti³ , M. Pfeuffer¹ ^, ² , U. Helwig⁴ , J. Herrmann¹ ^, ² , A. L. Fracanzani³ , P. Dongiovanni³ , S. Fargion³ , J. Schrezenmeir¹ ^, ² , D. Rubin⁴

¹Max Rubner-Institute, Federal Research Institute of Nutrition and Food, Department of Physiology and Biochemistry of Nutrition, Kiel, Germany
²Max Rubner-Institute, Federal Research Institute of Nutrition and Food, Department of Physiology and Biochemistry of Nutrition, Karlsruhe, Germany
³Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli Universita’ degli Studi di Milano, Ospedale Policlinico Mangialli e Regina Elena Fondazione IRCCS, Università di Milano, Milan, Italy
⁴University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Clinic for General Internal Medicine, I. Medical Department, Kiel, Germany

Abstract

The fatty acid transport protein 5 (FATP5) is exclusively expressed in the liver and is involved in hepatic lipid and bile metabolism. We investigated whether a variation in the FATP5 promoter (rs56225452) is associated with hepatic steatosis and further features of the metabolic syndrome. A total of 716 male subjects from the Metabolic Intervention Cohort Kiel (MICK) and 103 male subjects with histologically proved nonalcoholic fatty liver disease (NAFLD) were genotyped for this FATP5 polymorphism rs56225452 and phenotyped for features of the metabolic syndrome. In the MICK cohort, ALT activities, postprandial insulin, and triglyceride concentrations were higher in subjects carrying the rare A-allele compared to GG homozygotes. Accordingly, the insulin sensitivity index determined after a mixed meal and standardized glucose load was lower in A-allele carriers. NAFLD cases carrying allele A were presented with also higher ALT activities. In NAFLD subjects, the association of BMI with the degree of steatosis and glucose concentration differed across FATP5 promoter polymorphism. The FATP5 promoter polymorphism rs56225452 is associated with higher ALT activity, insulin resistance, and dyslipidemia in the general population. The impact of the BMI on the severity of steatosis in NAFLD cases seems to depend on the FATP5 polmorphism.

Key words

FATP5 - postprandial insulin resistance - hepatic steatosis - genetic variation

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References

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Correspondence

A. Auinger

Max Rubner-Institut

Federal Research Institute of

Nutrition and Food

Department of Physiology and

Biochemistry of Nutrition

Hermann-Weigmann-Straße 1

24103 Kiel

Germany

Telefon: +49/431/609 2506

Fax: +49/431/609 2472

eMail: Annegret.Auinger@mri.bund.de