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

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.