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

Ming Sheng Teng, Lung An Hsu, Semon Wu, Hsin Hua Chou, Chi Jen Chang, Yu Zen Sun, Shu Hui Juan, Yu Lin Ko

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalAtherosclerosis
Volume228
Issue number2
DOIs
Publication statusPublished - Jun 2013

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Selectins
Blood Group Antigens
HDL Cholesterol
Triglycerides
Genes
Genotype
P-Selectin
Genetic Markers
LDL Cholesterol
Population
Cardiovascular Diseases
Biomarkers
Cholesterol
Lipids

Keywords

  • ABO gene variants
  • Genetic association study
  • Inflammatory markers
  • Lipid profiles
  • Suppression effect
  • TG/HDL-C ratio

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level. / Teng, Ming Sheng; Hsu, Lung An; Wu, Semon; Chou, Hsin Hua; Chang, Chi Jen; Sun, Yu Zen; Juan, Shu Hui; Ko, Yu Lin.

In: Atherosclerosis, Vol. 228, No. 2, 06.2013, p. 406-412.

Research output: Contribution to journalArticle

Teng, Ming Sheng ; Hsu, Lung An ; Wu, Semon ; Chou, Hsin Hua ; Chang, Chi Jen ; Sun, Yu Zen ; Juan, Shu Hui ; Ko, Yu Lin. / Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level. In: Atherosclerosis. 2013 ; Vol. 228, No. 2. pp. 406-412.
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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.",
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T1 - Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level

AU - Teng, Ming Sheng

AU - Hsu, Lung An

AU - Wu, Semon

AU - Chou, Hsin Hua

AU - Chang, Chi Jen

AU - Sun, Yu Zen

AU - Juan, Shu Hui

AU - Ko, Yu Lin

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N2 - 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.

AB - 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.

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