title: I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders.
abstract: BACKGROUND
  The patatin-like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied.
  
  
  OBJECTIVE
  To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis.
  
  
  METHODS
  Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes.
  
  
  RESULTS
  Non-alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high-density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima-media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype.
  
  
  CONCLUSIONS
  PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic-related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: M-F
authors.initials: MF
authors.lastname: Xia
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Bian
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: H-D
authors.initials: HD
authors.lastname: Lin
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: H-M
authors.initials: HM
authors.lastname: Yan
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: X-X
authors.initials: XX
authors.lastname: Chang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: L-S
authors.initials: LS
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: S-S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: B-J
authors.initials: BJ
authors.lastname: Wu
authors.affiliation: Department of Ultrasonography, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: W-Y
authors.initials: WY
authors.lastname: He
authors.affiliation: Department of Health Statistics and Social Medicine, School of Public Health, Fudan University, Shanghai, China.
authors.forename: N-Q
authors.initials: NQ
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Chronic Metabolic Diseases, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Gao
mesh_terms: D000368:Aged; D000483:Alleles; D001786:Blood Glucose; D015992:Body Mass Index; D001837:Body Weights and Measures; D059168:Carotid Intima-Media Thickness; D002681:China; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D009765:Obesity / Q000503:physiopathology*; D010740:Phospholipases; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008049:Lipase; D008565:Membrane Proteins; D010740:Phospholipases; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent