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Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: results from the WELCOME trial

Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: results from the WELCOME trial
Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: results from the WELCOME trial
Background & Aims Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain. Methods One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15–18 months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome. Results Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I = 41, 148I/M = 43, 148M/M = 11; TM6SF2 E167K 167E/E = 78, 167E/K+167K/K = 17 participants) (mean ± SD age, 51 ± 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient −1.02 (95% CI −1.97, −0.07), p = 0.036) but not percentage of EPA enrichment (B coefficient −0.31 (95% CI −1.38, 0.75), p = 0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p = 0.008), but not end of study triglyceride concentration (B coefficient −0.11 (95% CI −0.64, 0.42), p = 0.68). Conclusions PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration.
0168-8278
1476-1483
Scorletti, Eleonora
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West, Annette L.
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Bhatia, Lokpal
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Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
McCormick, Keith
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Burdge, Graham C.
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Lillycrop, Karen A.
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Clough, Geraldine F.
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Calder, Philip C.
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Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Scorletti, Eleonora
5d46801d-a34a-453c-a3f5-86ebb6e20195
West, Annette L.
e8dacc1a-5fdc-4a4f-92d8-608f2ea2994c
Bhatia, Lokpal
41232d21-eef2-43a9-a129-994b81ccedaf
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
McCormick, Keith
95d56eea-74aa-4b48-b950-ab8207e57d08
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c

Scorletti, Eleonora, West, Annette L., Bhatia, Lokpal, Hoile, Samuel P., McCormick, Keith, Burdge, Graham C., Lillycrop, Karen A., Clough, Geraldine F., Calder, Philip C. and Byrne, Christopher D. (2015) Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: results from the WELCOME trial. Journal of Hepatology, 63 (6), 1476-1483. (doi:10.1016/j.jhep.2015.07.036). (PMID:26272871)

Record type: Article

Abstract

Background & Aims Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain. Methods One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15–18 months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome. Results Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I = 41, 148I/M = 43, 148M/M = 11; TM6SF2 E167K 167E/E = 78, 167E/K+167K/K = 17 participants) (mean ± SD age, 51 ± 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient −1.02 (95% CI −1.97, −0.07), p = 0.036) but not percentage of EPA enrichment (B coefficient −0.31 (95% CI −1.38, 0.75), p = 0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p = 0.008), but not end of study triglyceride concentration (B coefficient −0.11 (95% CI −0.64, 0.42), p = 0.68). Conclusions PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration.

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Accepted/In Press date: 27 July 2015
e-pub ahead of print date: 10 August 2015
Published date: December 2015
Organisations: Human Development & Health
Learn more about Biological Sciences research

Identifiers

Local EPrints ID: 379459
URI: http://eprints.soton.ac.uk/id/eprint/379459
DOI: doi:10.1016/j.jhep.2015.07.036
ISSN: 0168-8278
PURE UUID: cab114b7-979b-4e88-b930-f3088ad5f19b
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Geraldine F. Clough: ORCID iD orcid.org/0000-0002-6226-8964
ORCID for Philip C. Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 28 Jul 2015 13:16
Last modified: 15 Mar 2024 03:02

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Contributors

Author: Eleonora Scorletti
Author: Annette L. West
Author: Lokpal Bhatia
Author: Samuel P. Hoile
Author: Keith McCormick
Author: Graham C. Burdge ORCID iD
Author: Karen A. Lillycrop ORCID iD
Author: Geraldine F. Clough ORCID iD
Author: Philip C. Calder ORCID iD
Author: Christopher D. Byrne ORCID iD

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