Chi-Ming Tai1, Chih-Kun Huang2, Hung-Pin Tu3, Jau-Chung Hwang4, Chi-Yang Chang5, Ming-Lung Yu6. 1. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Bariatric and Metabolic International Surgery Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. 2. Bariatric and Metabolic International Surgery Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. 3. Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Department of Pathology, Lin Shin Hospital, Taichung, Taiwan. 5. Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. 6. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Center and Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.
Abstract
BACKGROUND: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with histologic disease severity in patients with nonalcoholic fatty liver disease (NAFLD); however, whether the PNPLA3 genotype has an effect on susceptibility of nonalcoholic steatohepatitis (NASH) from NAFLD among severely obese patients remains unclear. The objective of this study was to investigate the role of the PNPLA3 genotype on NASH in severely obese Asian patients with NAFLD. METHODS: The PNPLA3 rs738409 genotype was determined in 181 severely obese patients who underwent bariatric surgery. The diagnosis of NASH and the NAFLD activity score (NAS) were determined by liver histopathology. RESULTS: Of the 181 patients, 29 (16.0%), 60 (33.2%), and 92 (50.8%) were in the non-NAFLD, steatosis, and NASH groups, respectively. The PNPLA3 rs738409 GG genotype was associated with higher liver enzymes and a higher risk for NASH (odds ratio [OR], 3.72; 95% CI, 1.25-11.05). The GG genotype was also associated with histologic severity of NAFLD, including higher steatosis grade (OR, 9.94; 95% CI, 2.20-44.83 for patients with grade 3 steatosis) and NAS (OR, 11.49; 95% CI, 2.50-52.83 for patients with a NAS ≥5). Finally, multiple logistic regression also showed that the GG genotype was an independent risk factor for NASH (OR, 3.58; 95% CI, 1.15-11.12) in NAFLD patients. CONCLUSION: The PNPLA3 rs738409 GG genotype increases susceptibility of NASH in severely obese Asians with NAFLD and correlates to histologic severity of NAFLD.
BACKGROUND: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with histologic disease severity in patients with nonalcoholic fatty liver disease (NAFLD); however, whether the PNPLA3 genotype has an effect on susceptibility of nonalcoholic steatohepatitis (NASH) from NAFLD among severely obesepatients remains unclear. The objective of this study was to investigate the role of the PNPLA3 genotype on NASH in severely obese Asian patients with NAFLD. METHODS: The PNPLA3rs738409 genotype was determined in 181 severely obesepatients who underwent bariatric surgery. The diagnosis of NASH and the NAFLD activity score (NAS) were determined by liver histopathology. RESULTS: Of the 181 patients, 29 (16.0%), 60 (33.2%), and 92 (50.8%) were in the non-NAFLD, steatosis, and NASH groups, respectively. The PNPLA3rs738409 GG genotype was associated with higher liver enzymes and a higher risk for NASH (odds ratio [OR], 3.72; 95% CI, 1.25-11.05). The GG genotype was also associated with histologic severity of NAFLD, including higher steatosis grade (OR, 9.94; 95% CI, 2.20-44.83 for patients with grade 3 steatosis) and NAS (OR, 11.49; 95% CI, 2.50-52.83 for patients with a NAS ≥5). Finally, multiple logistic regression also showed that the GG genotype was an independent risk factor for NASH (OR, 3.58; 95% CI, 1.15-11.12) in NAFLD patients. CONCLUSION: The PNPLA3rs738409 GG genotype increases susceptibility of NASH in severely obese Asians with NAFLD and correlates to histologic severity of NAFLD.
Authors: Gemma Aragonès; Teresa Auguet; Sandra Armengol; Alba Berlanga; Esther Guiu-Jurado; Carmen Aguilar; Salomé Martínez; Fátima Sabench; José Antonio Porras; Maikel Daniel Ruiz; Mercé Hernández; Joan Josep Sirvent; Daniel Del Castillo; Cristóbal Richart Journal: Int J Mol Sci Date: 2016-04-27 Impact factor: 5.923