title: Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level.
abstract: OBJECTIVE
  Previous investigations have revealed an association between the ABO locus/blood group and total cholesterol and inflammatory biomarker levels. We aimed to test the statistical association of ABO locus variants with lipid profiles and levels of thirteen inflammatory markers in a Taiwanese population.
  
  
  RESULTS
  A sample population of 617 Taiwanese subjects was enrolled. Five ABO gene region polymorphisms were selected and genotyped. After adjusting for clinical covariates and inflammatory marker levels, the genetic-inferred ABO blood group genotypes were associated with sE-selectin level (P = 3.5 × 10(-36)). Significantly higher total and low-density lipoprotein cholesterol (LDL-C) levels were noted in individuals with blood group A (P = 7.2 × 10(-4) and P = 7.3 × 10(-4), respectively). Interestingly, after adjusting for sE-selectin level, significantly lower high-density lipoprotein cholesterol (HDL-C) level as well as higher triglyceride (TG) level and ratio of triglyceride to HDL-C (TG/HDL-C ratio) were noted in individuals with blood group A comparing to non-A individuals (P = 0.009, P = 0.004 and P = 0.001, respectively); these associations were also observed in the group A male subjects (P = 0.027, P = 0.001, and P = 0.002, respectively). Mediation analysis further revealed a suppression effect of sE-selectin level on the association between genetic-inferred ABO blood group genotypes and TG/HDL-C ratio in total participants (P = 1.18 × 10(-6)) and in males (P = 5.99 × 10(-5)).
  
  
  CONCLUSIONS
  Genetic variants at the ABO locus independently affect sE-selectin level in Taiwanese subjects, while the association of ABO locus variants with TG/HDL-C ratio is suppressed by sE-selectin level in Taiwanese males. These results provided further evidence for the mechanism in the association of ABO blood groups with atherosclerotic cardiovascular diseases.
authors.affiliation: Graduate Institute of Medical Sciences, Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Teng
authors.forename: Lung-An
authors.initials: LA
authors.lastname: Hsu
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chou
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chang
authors.forename: Yu-Zen
authors.initials: YZ
authors.lastname: Sun
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Juan
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Ko
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D019040:E-Selectin / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood*
chemical_list: D000017:ABO Blood-Group System; D015415:Biomarkers; D008076:Cholesterol, HDL; D019040:E-Selectin; D018836:Inflammation Mediators; C546936:SELE protein, human; D014280:Triglycerides