Reply to: “The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort”

Stephen R. Atkinson; Michael J. Way; Andrew McQuillin; Marsha Y. Morgan; Mark R. Thursz

doi:10.1016/j.jhep.2017.12.005

Letter to the Editor| Volume 68, ISSUE 4, P860-862, April 2018

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Reply to: “The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort”

Stephen R. Atkinson
Stephen R. Atkinson
Correspondence
Corresponding author. Address: Department of Hepatology, 10th Floor QEQM, St Marys’ Hospital, London W2 1NY, UK. Tel.: +44 20 3312 6454; fax: +44 20 7724 9369.
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Department of Hepatology, Division of Surgery and Cancer, Imperial College London, UK
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Michael J. Way
Michael J. Way
Affiliations
UCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK
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Andrew McQuillin
Andrew McQuillin
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Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK
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Marsha Y. Morgan ^†
Author Footnotes
† Joint senior authors.
Marsha Y. Morgan
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† Joint senior authors.
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UCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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Mark R. Thursz ^†
Author Footnotes
† Joint senior authors.
Mark R. Thursz
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† Joint senior authors.
Affiliations
Department of Hepatology, Division of Surgery and Cancer, Imperial College London, UK
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† Joint senior authors.

Published:December 11, 2017DOI:https://doi.org/10.1016/j.jhep.2017.12.005

We thank Meffert and co-workers

^[1]

Meffert P.J.
Repp K.D.
Völzke H.
Weiss F.U.
Homuth G.
Kühn J.P.

The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population based cohort.

for their interest in our study and for providing data which support our finding of an association between carriage of rs738409:G in patatin-like phospholipase domain-containing 3 (PNPLA3) and the risk of liver-associated mortality, at least in men.

^[2]

Atkinson S.R.
Way M.J.
McQuillin A.
Morgan M.Y.
Thursz M.R.

Homozygosity for rs738409: G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis.

The authors evaluated the association of rs738409:G with mortality in adults participating in a population-based health study in Pomerania. The included population of 4,081 was sub-classified by sex and by the absence/presence of hepatic steatosis on ultrasound. Participants were censored at death or when lost to follow-up with the length of follow-up defined as birth to censorship. The median follow-up period was 11.3 (interquartile range: 10.6–11.8) years, though this is difficult to equate with the definition of the follow-up period provided. In men, carriage of rs738409:G was associated with a fourfold increase in the hazard of liver-disease-related mortality; there were too few events in women for analysis. These data corroborate not only our findings that carriage of rs738409:G is a negative risk factor for survival,

^[2]

Atkinson S.R.
Way M.J.
McQuillin A.
Morgan M.Y.
Thursz M.R.

Homozygosity for rs738409: G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis.

but also the reported association with a reduction in survival in people listed for liver transplantation

^[3]

Friedrich K.
Wannhoff A.
Kattner S.
Brune M.
Hov J.R.
Weiss K.H.
et al.

PNPLA3 in end-stage liver disease: alcohol consumption, hepatocellular carcinoma development, and transplantation-free survival.

and in those with cirrhosis and hepatocellular carcinoma.

^[4]

Valenti L.
Motta B.M.
Soardo G.
Iavarone M.
Donati B.
Sangiovanni A.
et al.

PNPLA3 I148M polymorphism, clinical presentation, and survival in patients with hepatocellular carcinoma.

The authors also showed that, in men, carriage of rs738409:G was associated with a decrease in the risk of death from coronary artery disease; there was no such effect in women.

^[1]

Meffert P.J.
Repp K.D.
Völzke H.
Weiss F.U.
Homuth G.
Kühn J.P.

The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population based cohort.

Liu and colleagues

^[5]

Liu D.J.
Peloso G.M.
Yu H.
Butterworth A.S.
Wang X.
Mahajan A.
et al.

Exome-wide association study of plasma lipids in >300,000 individuals.

recently reported in an exome-wide association study in >300,000 individuals that carriage of rs738409:G was associated with a lower risk of coronary artery disease, corroborating this finding, although sex-specific data were not provided.

Keywords

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Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis
Journal of HepatologyVol. 67Issue 1
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  Cirrhosis is a major cause of global mortality, accounting for around one million deaths per annum.¹ Alcohol misuse is the leading cause of cirrhosis in the Western world and is implicated in almost half of cirrhosis-related deaths.²
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The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort
Journal of HepatologyVol. 68Issue 4
- Preview
  In a recent issue of the Journal, Atkinson and co-workers reported that a variant in the gene patatin-like phospholipase domain-containing 3 (PNPLA3) not only affects liver disease susceptibility but also mortality following episodes of severe alcoholic hepatitis.¹ Individuals carrying the rs738409C>G (I148M) single nucleotide polymorphism (SNP) of PNPLA3 have previously been reported to accumulate lipids in the liver, to have a higher prevalence of liver disease² and to be at an increased risk of developing steatohepatitis and cirrhosis.
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Reply to: “The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort”

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