title: MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study.
abstract: BACKGROUND
  Microsomal triglyceride transfer protein (MTP) works to lipidate and assemble the apoB-containing lipoproteins in liver. It closely links up the hepatic secretion of lipid to regulate serum lipid and atherosclerosis. Cases of MTTP gene mutation is characterized by abetalipoproteinemia and remarkable hepatic steatosis or cirrhosis. Several MTTP polymorphisms have been reported relating to metabolic syndrome, hyperlipidemia and steatohepatitis. We supposed the regulation of serum lipids and risk of non-alcoholic fatty liver disease (NAFLD) formation may be modified by individual susceptibility related to the MTTP polymorphisms.
  
  
  RESULTS
  A cross-sectional population of 1193 subjects, 1087 males and 106 females mean aged 45.9 ± 8.9 years, were enrolled without recognized secondary hyperlipidemia. Fasting serum lipid, insulin, and non-esterified fatty acid were assessed and transformed to insulin resistance index, HOMA-IR and Adipo-IR. After ruling out alcohol abuser, non-alcoholic fatty liver disease (NAFLD) was diagnosed by abdominal ultrasound. Five common MTTP polymorphisms (promoter -493 G/T, E98D, I128T, N166S, and Q297H) were conducted by TaqMan assay. Multivariate regression analysis was used to estimate their impact on serum lipid and NAFLD risk. Assessment revealed a differential impact on LDL-C and non-HDL-C, which were sequentially determined by the Q297H polymorphism, insulin resistance, body mass index and age. Carriers of homozygous minor allele (297 H) had significantly lower LDL-C and non-HDL-C but higher risk for NAFLD. Molecular modeling of the 297 H variant demonstrated higher free energy, potentially referring to an unstable structure and functional sequence.
  
  
  CONCLUSIONS
  These results evidenced the MTTP polymorphisms could modulate the lipid homeostasis to determine the serum lipids and risk of NAFLD. The MTTP 297 H polymorphism interacted with age, insulin resistance and BMI to decrease serum apoB containing lipoproteins (LDL-C and non-HDL-C) but increase the risk of NAFLD formation.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine; Kaohsiung Municipal Siaogang Hospital, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. pjhsiao@kmu.edu.tw.|School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung, 807, Taiwan. pjhsiao@kmu.edu.tw.
authors.forename: Pi-Jung
authors.initials: PJ
authors.lastname: Hsiao
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine; Kaohsiung Municipal Siaogang Hospital, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. lovellelee@hotmail.com.
authors.forename: Mei-Yueh
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. c00jsw00@kmu.edu.tw.
authors.forename: Yeng-Tseng
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine; Kaohsiung Municipal Siaogang Hospital, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 960219@gmail.com.
authors.forename: He-Jiun
authors.initials: HJ
authors.lastname: Jiang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine; Kaohsiung Municipal Siaogang Hospital, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. pichili@kmu.edu.tw.
authors.forename: Pi-Chen
authors.initials: PC
authors.lastname: Lin
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. yihsya@kmu.edu.tw.
authors.forename: Yi-Hsin Connie
authors.initials: YH
authors.lastname: Yang
authors.affiliation: School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung, 807, Taiwan. kuoksfo@yahoo.com.tw.|Division of Hepatobiliopancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. kuoksfo@yahoo.com.tw.
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D014463:Ultrasonography
chemical_list: D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol