title: Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population.
abstract: BACKGROUND
  Apolipoprotein E (APOE) plays a major role in lipid metabolism and inflammation. However, the association between APOE gene polymorphisms and serum triglyceride levels remains controversial. We tested the effects of APOE variants on triglyceride levels and their interactions with the inflammatory marker C-reactive protein (CRP) in a Taiwanese population.
  
  
  METHODS
  Two APOE single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped by TaqMan Assay using real time PCR in 595 healthy subjects attending the clinic for routine visits.
  
  
  RESULTS
  After adjustment for clinical covariates, subjects carrying the rs429358-TT genotype and non-ε4 alleles were found to have higher CRP levels, whereas those with rs7412-CC genotype and non-ε2 alleles had significantly higher total and low-density lipoprotein cholesterol levels (all P < 0.01). Using subgroup and interaction analyses, we observed significantly lower triglyceride levels in subjects carrying the rs429358-TT genotype and non-ε4 alleles in the low CRP group (P = 2.71 × 10(-4) and P = 4.32 × 10(-4), respectively), but not in those in the high CRP group (interaction P = 0.013 and 0.045, respectively). In addition, multivariate stepwise linear regression analysis showed that subjects carrying the rs429358-TT genotype and non-ε4 alleles with low CRP levels had significantly lower triglyceride levels (P < 0.001 and P < 0.001, respectively). In addition, when combined with the risk alleles of GCKR, APOA5 and LPL gene variants, we observed that triglyceride levels increased significantly with the number of risk alleles (P = 2.9 × 10(-12)).
  
  
  CONCLUSIONS
  The combination of SNPs and ε alleles at the APOE locus is involved in managing lipid and CRP levels in the Taiwanese population. APOE polymorphisms interact with CRP to regulate triglyceride levels, thus triglyceride concentration is influenced by both the genetic background of the APOE locus and the inflammatory status of a subject.
authors.affiliation: Department of Life Science, Chinese Culture University, Taipei, Taiwan.|Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, New Taipei City, Taiwan.
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.affiliation: The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Lung-An
authors.initials: LA
authors.lastname: Hsu
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, New Taipei City, Taiwan.
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Teng
authors.affiliation: The Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, 289 Jianguo Road, Xindian District, New Taipei City, 231, Taiwan.
authors.forename: Jeng-Feng
authors.initials: JF
authors.lastname: Lin
authors.affiliation: The Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, 289 Jianguo Road, Xindian District, New Taipei City, 231, Taiwan.
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chou
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, New Taipei City, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, New Taipei City, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, New Taipei City, Taiwan.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Su
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, New Taipei City, Taiwan. yulinkotw@yahoo.com.tw.|The Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical foundation, 289 Jianguo Road, Xindian District, New Taipei City, 231, Taiwan. yulinkotw@yahoo.com.tw.|School of Medicine, Tzu Chi University, Hualien, Taiwan. yulinkotw@yahoo.com.tw.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Ko
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000072040:Apolipoprotein A-V / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D014280:Triglycerides / Q000097:blood* / Q000235:genetics
chemical_list: C437704:APOA5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000072040:Apolipoprotein A-V; D001057:Apolipoproteins E; D015415:Biomarkers; C485100:GCKR protein, human; D008055:Lipids; D014280:Triglycerides; D002097:C-Reactive Protein; C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: APOE; C-reactive protein (CRP); Gene association study; Gene–trait interaction; Polymorphism