Apolipoprotein E E3/E4 genotype is associated with an increased risk of premature coronary artery disease
Youqian Li1,2, Wei Zhong3,4, Changjing Huang3,4
1Center for Cardiovascular Diseases, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, China. d_yoyo@163.com.
Insights
The APOE ɛ3/ɛ4 genotype and smoking history are significant risk factors for premature coronary artery disease (PCAD). Overweight individuals also face an increased risk of developing PCAD.
Area of Science:
- Genetics and Cardiovascular Health
- Molecular Epidemiology
- Biochemistry of Lipids
Background:
- Dyslipidemia is a known contributor to coronary artery disease (CAD).
- Apolipoprotein E (APOE) gene polymorphism influences lipid levels, but its association with premature CAD (PCAD) risk remains debated.
- Understanding these genetic links is crucial for identifying at-risk populations.
Purpose of the Study:
- To investigate the relationship between APOE gene polymorphisms and the risk of premature CAD (PCAD).
- To specifically evaluate this association within the Hakka population.
- To identify independent risk factors for PCAD.
Main Methods:
- Retrospective analysis of 301 PCAD patients and 402 age-matched controls.
- Genotyping of APOE rs429358 and rs7412 polymorphisms using PCR-chip technique.
- Logistic regression analysis to determine associations between genotypes, alleles, and PCAD risk.
Main Results:
- The APOE ɛ3/ɛ4 genotype and ε4 allele were more frequent in PCAD patients compared to controls.
- Higher BMI (≥24.0 kg/m²), smoking history, APOE ɛ3/ɛ4 genotype, and total cholesterol (TC) levels were significantly associated with PCAD.
- Specific allele associations were observed with triglyceride (TG), HDL-C, and LDL-C levels.
Conclusions:
- BMI ≥ 24.0 kg/m², smoking history, APOE ɛ3/ɛ4 genotype, and TC level are independent risk factors for PCAD.
- Individuals who are overweight, smoke, and carry the APOE ɛ3/ɛ4 genotype have a heightened risk of PCAD.
- These findings highlight the importance of genetic predisposition and lifestyle factors in PCAD development.
Objective:
Dyslipidemia is one of the causes of coronary heart disease (CAD), and apolipoprotein E (APOE) gene polymorphism affects lipid levels. However, the relationship between APOE gene polymorphisms and premature CAD (PCAD, male CAD patients with ≤ 55 years old and female with ≤ 65 years old) risk had different results in different studies. The aim of this study was to assess this relationship and to further evaluate the relationship between APOE gene polymorphisms and PCAD risk in the Hakka population.
Methods:
This study retrospectively analyzed 301 PCAD patients and 402 age matched controls without CAD. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) -chip technique. The distribution of APOE genotypes and alleles between the case group and the control group was compared. The relationship between APOE genotypes and PCAD risk was obtained by logistic regression analysis.
Results:
The frequency of the APOE ɛ3/ɛ4 genotype (18.9% vs. 10.2%, p = 0.001) and ε4 allele (11.1% vs. 7.0%, p = 0.007) was higher in the PCAD patients than that in controls, respectively. PCAD patients with ɛ2 allele had higher TG level than those with ɛ3 allele, and controls carried ɛ2 allele had higher HDL-C level and lower LDL-C level than those carried ɛ3 allele. Regression logistic analysis showed that BMI ≥ 24.0 kg/m2 (BMI ≥ 24.0 kg/m2 vs. BMI 18.5-23.9 kg/m2, OR: 1.763, 95% CI: 1.235-2.516, p = 0.002), history of smoking (Yes vs. No, OR: 5.098, 95% CI: 2.910-8.930, p < 0.001), ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 2.203, 95% CI: 1.363-3.559, p = 0.001), ε4 allele (ε4 vs. ε3, OR: 2.125, 95% CI: 1.333-3.389, p = 0.002), and TC level (OR: 1.397, 95% CI: 1.023-1.910, p = 0.036) were associated with PCAD.
Conclusions:
In summary, BMI ≥ 24.0 kg/m2, history of smoking, APOE ɛ3/ɛ4 genotype, and TC level were independent risk factors for PCAD. It means that young individuals who are overweight, have a history of smoking, and carried APOE ɛ3/ɛ4 genotype had increased risk of PCAD.
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