Alimentary Pharmacology and Therapeutics

Letters to the Editors Letter: PNPLA3 and alcoholic liver disease - an alert to methodological limitations

dling of DNA strands, and of the two alleles under study, the present meta-analysis calls for extensive remastering.

P. G. Sand*,†

ACKNOWLEDGEMENT Declaration of personal and funding interests: None.

*Department of Psychiatry, University of Regensburg, Regensburg, Germany. † Danuvius Klinik GmbH, Ingolstadt, Germany. E-mail: [email protected]

REFERENCES

doi:10.1111/apt.13070

SIRS, I read with interest the recent paper by Chamorro and coworkers1 on the putative effects of a PNPLA3 variant, rs738409, in the context of alcoholic liver cirrhosis. The authors conclude a significant risk enhancing role of the G allele on the grounds of 11 earlier case–control studies. I voice concerns, however, over the approach taken to pooling the association data currently available. Not only do the numbers given differ from those previously published,2, 3 with regard to the majority of studies consulted, the authors could not possibly tell whether the at risk-allele was meant to be ‘C’ or rather ‘G’, as genetic exposure was not specified in the original articles.3–8 For differentiation of the two alleles, DNA strand information is essential if the ‘G’ allele is not to be mistaken for the ‘C’ allele and vice versa. In those cases where strand information was actually provided, this was ignored by the authors leading to post hoc misassignment of the risk enhancing and protective alleles. Thus, the study by Falleti et al.2 examined the nontranscribed DNA strand, but was treated by Chamorro et al. as having addressed the transcribed strand as in the study by Rosendahl et al.9 Owing to continued mud-

1. Chamorro AJ, Torres JL, Mir onCanelo JA, et al. Systematic review with metaanalysis: the I148M variant of patatinlike phospholipase domaincontaining 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis. Aliment Pharmacol Ther 2014; 40: 571–81. 2. Falleti E, Fabris C, Cmet S, et al. PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence. Liver Int 2011; 31: 1137–43. 3. Way MJ, Morgan M. The Pnpla3 I148m mutation significantly increases the risk of developing alcoholrelated cirrhosis in alcohol dependent individuals. Alcohol Alcohol 2013; 48: 37–37. 4. Seth D, Daly AK, Haber PS, et al. Patatinlike phospholipase domain containing 3: a case in point linking genetic susceptibility for alcoholic and nonalcoholic liver disease. Hepatology 2010; 51: 1463–5. 5. Nischalke HD, Berger C, Luda C, et al. The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis. PLoS ONE 2011; 6: e27087. 6. NguyenKhac E, Houchi H, Dreher ML, et al. Is PNPLA3 polymorphism involved in severe acute alcoholic hepatitis. Hepatology 2011; 54: 976A. 7. Trepo E, Gustot T, Degre D, et al. Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease. J Hepatol 2011; 55: 906–12. 8. Stickel F, Buch S, Lau K, et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology 2011; 53: 86–95. 9. Rosendahl J, Tonjes A, Schleinitz D, et al. A common variant of PNPLA3 (p I148M) is not associated with alcoholic chronic pancreatitis. PLoS ONE 2012; 7: e29433.

AP&T invited editorial and correspondence columns are restricted to letters discussing papers that have been published in the journal. A letter must have a maximum of 300 words, may contain one table or figure, and should have no more than 10 references. It should be submitted electronically to the Editors via http://mc.manuscriptcentral.com/apt.

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Letter: PNPLA3 and alcoholic liver disease--an alert to methodological limitations.

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