{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:58:34Z","timestamp":1793149114214,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: weight loss as a result of lifestyle intervention is effective when treating non-alcoholic fatty liver disease (NAFLD). We estimated the effects of PNPLA3 rs738409 and HSD17B13 rs6834314 variants in response to diet therapy in Japanese patients with NAFLD. Methods: we analyzed the correlation between the change in liver stiffness and change in body weight in 140 patients administered diet therapy for 1-year, according to PNPLA3 and HSD17B13 genotypes. Results: the bodyweight (BW) reduction rate was greater in patients with the PNPLA3 genotype CC than CG and GG (p = 0.035). Change in liver stiffness measurement (LSM) was significantly associated with a change in BW in PNPLA3 CG\/GG (r = 0.279\/0.381), but not in PNPLA3 CC (p = 0.187). Change in LSM was correlated with change in BW only in patients with HSD17B13 AG\/GG (r = 0.425), but not the AA genotype (p = 0.069). A multivariate analysis identified that a change in LSM was correlated with a change in BW in carriers of HSD17B13 AG\/GG (B = 3.043, p = 0.032), but not HSD17B13 AA. The change in LSM of patients with a BW reduction of more than 7% (0.50) was significantly greater than that of patients with a BW reduction of less than 7% (0.83) (p = 0.038). Conclusions: in Japanese patients with NAFLD, HSD17B13 rs6834314 polymorphism is associated with the change in LSM by lifestyle intervention. The approach, including genetic assessments, may contribute to the establishment of appropriate therapeutic strategies to treat NAFLD.<\/jats:p>","DOI":"10.3390\/genes12050628","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Effect of Genetic Polymorphism in Response to Body Weight Reduction in Japanese Patients with Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-5894","authenticated-orcid":false,"given":"Yuya","family":"Seko","sequence":"first","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0631-046X","authenticated-orcid":false,"given":"Kanji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Tochiki","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Okishio","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seita","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiroh","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihisa","family":"Moriguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-3635","authenticated-orcid":false,"given":"Yoshito","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.25762","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association","volume":"55","author":"Chalasani","year":"2012","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s00535-015-1050-7","article-title":"Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis","volume":"50","author":"Watanabe","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","article-title":"Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease","volume":"149","author":"Angulo","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/hep.23276","article-title":"Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis","volume":"51","author":"Promrat","year":"2010","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1002\/hep.24242","article-title":"Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects","volume":"53","author":"Haufe","year":"2011","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jhep.2013.04.013","article-title":"Community-based lifestyle modification programme for non-alcoholic fatty liver disease: A randomized controlled trial","volume":"59","author":"Wong","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.jhep.2017.05.016","article-title":"Treatment of NAFLD with diet, physical activity and exercise","volume":"67","author":"Trenell","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1053\/j.gastro.2010.07.057","article-title":"Genome-wide association study identifies variants associated with histologic features of nonalcoholic fatty liver disease","volume":"139","author":"Chalasani","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kawaguchi, T., Sumida, Y., Umemura, A., Matsuo, K., Takahashi, M., Takamura, T., Yasui, K., Saibara, T., Hashimoto, E., and Kawanaka, M. (2012). Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038322"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ajhg.2008.09.012","article-title":"Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes","volume":"83","author":"Yuan","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/hepr.12840","article-title":"Development of hepatocellular carcinoma in Japanese patients with biopsy-proven non-alcoholic fatty liver disease: Association between PNPLA3 genotype and hepatocarcinogenesis\/fibrosis progression","volume":"47","author":"Seko","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/ajg.2013.476","article-title":"The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: A meta-analysis","volume":"109","author":"Singal","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa1712191","article-title":"A protein-truncating HSD17B13 variant and protection from chronic liver disease","volume":"378","author":"Cheng","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/hep.30623","article-title":"A HSD17B13 variant protects from hepatocellular carcinoma development in alcoholic liver disease","volume":"70","author":"Yang","year":"2019","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1002\/hep.30350","article-title":"17-Beta hydroxysteroid dehydrogenase 13 is a hepatic retinol dehydrogenase associated with histological features of nonalcoholic fatty liver disease","volume":"69","author":"Ma","year":"2019","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1111\/liv.14495","article-title":"Attenuated effect of PNPLA3 on hepatic fibrosis by HSD17B13 in Japanese patients with non-alcoholic fatty liver disease","volume":"40","author":"Seko","year":"2020","journal-title":"Liver Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3945\/ajcn.111.012369","article-title":"Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans","volume":"94","author":"Sevastianova","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/jgh.12656","article-title":"PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease","volume":"30","author":"Shen","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Giuffr\u00e9, M., Colecchia, A., and Croc\u00e9, L.S. (2020). Elastography: Where are we now?. Minerva Gastroenterol. Dietol.","DOI":"10.23736\/S2724-5985.20.02773-7"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Giuffr\u00e8, M., Giuricin, M., Bonazza, D., Rosso, N., Giraudi, P.J., Masutti, F., Palmucci, S., Basile, A., Zanconati, F., and de Manzini, N. (2020). Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery. Diagnostics, 7.","DOI":"10.3390\/diagnostics10100795"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.aohep.2020.04.003","article-title":"Is there an association between commonly employed biomarkers of liver fibrosis and liver stiffness in the general population?","volume":"19","author":"Foschi","year":"2020","journal-title":"Ann. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/S0016-5085(99)70506-8","article-title":"Nonalcoholic fatty liver diseases: A spectrum of clinical and pathological severity","volume":"116","author":"Matteoni","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00125-011-2446-4","article-title":"Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of randomised trials","volume":"55","author":"Musso","year":"2012","journal-title":"Diabetologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E146","DOI":"10.1111\/hepr.12552","article-title":"Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus","volume":"46","author":"Kan","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1016\/j.soard.2016.06.004","article-title":"PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery","volume":"12","author":"Krawczyk","year":"2016","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Palmer, C.N., Maglio, C., Pirazzi, C., Burza, M.A., Adiels, M., Burch, L., Donnelly, L.A., Colhoun, H., Doney, A.S., and Dillon, J.F. (2012). Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039362"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/ng.970","article-title":"Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma","volume":"43","author":"Chambers","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1053\/j.gastro.2009.06.005","article-title":"Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors","volume":"137","author":"Kotronen","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1053\/j.gastro.2008.01.075","article-title":"Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects","volume":"134","author":"Korenblat","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1053\/j.gastro.2008.03.021","article-title":"Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes","volume":"135","author":"Kotronen","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Giuffr\u00e8, M., Fouraki, S., Comar, M., Masutti, F., and Croc\u00e8, L.S. (2020). The Importance of Transaminases Flare in Liver Elastography: Characterization of the Probability of Liver Fibrosis Overestimation by Hepatitis C Virus-Induced Cytolysis. Microorganisms, 29.","DOI":"10.3390\/microorganisms8030348"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s40477-020-00456-9","article-title":"Alanine aminotransferase and spleno-portal dynamics affect spleen stiffness measured by point shear-wave elastography in patients with chronic hepatitis C in the absence of significant liver fibrosis","volume":"24","author":"Fouraki","year":"2021","journal-title":"J. Ultrasound"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.aohep.2020.07.004","article-title":"Spleen stiffness can be employed to assess the efficacy of spontaneous portosystemic shunts in relieving portal hypertension","volume":"19","author":"Bedogni","year":"2020","journal-title":"Ann. Hepatol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/5\/628\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:51:30Z","timestamp":1760161890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/5\/628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,22]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["genes12050628"],"URL":"https:\/\/doi.org\/10.3390\/genes12050628","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,22]]}}}