title: PNPLA3 I148M variant in nonalcoholic fatty liver disease: demographic and ethnic characteristics and the role of the variant in nonalcoholic fatty liver fibrosis.
abstract: Patatin-like phospholipase domain-containing 3 (PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism, and has been reported to be significantly associated with liver fat content. Various studies have established a strong link between the 148 isoleucine to methionine protein variant (I148M) of PNPLA3 and liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, detailed demographic and ethnic characteristics of the I148M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated. The present review summarizes the current knowledge on the association between the PNPLA3 I148M variant and NAFLD, and especially its role in the development of nonalcoholic fatty liver fibrosis. First, we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148M variant and the presence of metabolic syndrome on the association between PNPLA3 I148M and NAFLD. Then, we explore the role of the PNPLA3 I148M in the development of nonalcoholic fatty liver fibrosis, and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network. Finally, we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148M variant in fibrogenesis, which, in turn, provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.
authors.affiliation: Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.affiliation: Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Xin
authors.affiliation: Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Geng
authors.affiliation: Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
authors.forename: Ding-Ding
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Xuan
mesh_terms: D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Nonalcoholic fatty liver disease; Nonalcoholic fatty liver fibrosis; PNPLA3 I148M variant; Polymorphism