Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level

Atherosclerosis. 2013 Jun;228(2):406-12. doi: 10.1016/j.atherosclerosis.2013.03.032. Epub 2013 Apr 8.

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.

Methods and 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)).

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / genetics*
  • Adult
  • Asian People / genetics
  • Atherosclerosis / blood*
  • Atherosclerosis / epidemiology
  • Atherosclerosis / genetics*
  • Atherosclerosis / immunology
  • Biomarkers / blood
  • Cholesterol, HDL / blood*
  • Cross-Sectional Studies
  • Down-Regulation
  • E-Selectin / blood*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Taiwan / epidemiology
  • Triglycerides / blood*

Substances

  • ABO Blood-Group System
  • Biomarkers
  • Cholesterol, HDL
  • E-Selectin
  • Inflammation Mediators
  • SELE protein, human
  • Triglycerides