Key result
The LDLR rs2228671-T allele was significantly associated with a reduced risk of coronary heart disease (OR 0.83; 95% CI 0.75-0.92; P=0.0005), though this protective effect was absent in Han Chinese.
Why the study?
Is the LDLR rs2228671 polymorphism associated with the risk of coronary heart disease?
Meta-Analysis (n=17,299)
Yes
Is the LDLR rs2228671 polymorphism associated with the risk of coronary heart disease?
Odds Ratio: 0.83 (95% CI 0.75–0.92)
p-value: p=0.0005
The LDLR rs2228671-T allele is a protective genetic factor against coronary heart disease in European populations, but this association is absent in Han Chinese due to ethnic differences in allele frequency.
Ethnic differences limit LDLR rs2228671 generalizability for CHD risk; leaves open ancestry-specific validation studies.
Low density lipoprotein receptor (LDLR) can regulate cholesterol metabolism by removing the excess low density lipoprotein cholesterol (LDL-C) in blood. Since cholesterol metabolism is often disrupted in coronary heart disease (CHD), LDLR as a candidate gene of CHD has been intensively studied. The goal of our study is to evaluate the overall contribution of LDLR rs2228671 polymorphism to the risk of CHD by combining the genotyping data from multiple case-control studies. Our meta-analysis is involved with 8 case-control studies among 7588 cases and 9711 controls to test the association between LDLR rs2228671 polymorphism and CHD. In addition, we performed a case-control study of LDLR rs2228671 polymorphism with the risk of CHD in Chinese population. Our meta-analysis showed that rs2228671-T allele was significantly associated with a reduced risk of CHD (P = 0.0005, odds ratio (OR) = 0.83, and 95% confidence interval (95% CI) = 0.75-0.92). However, rs2228671-T allele frequency was rare (1%) and was not associated with CHD in Han Chinese (P = 0.49), suggesting an ethnic difference of LDLR rs2228671 polymorphism. Meta-analysis has established rs2228671 as a protective factor of CHD in Europeans. The lack of association in Chinese reflects an ethnic difference of this genetic variant between Chinese and European populations.
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Ye et al. (2014) conducted a meta-analysis in Coronary Heart Disease (n=17,299). LDLR rs2228671-T allele vs. Reference allele was evaluated on Risk of coronary heart disease (OR 0.83, 95% CI 0.75-0.92, p=0.0005). The LDLR rs2228671-T allele was significantly associated with a reduced risk of coronary heart disease (OR 0.83; 95% CI 0.75-0.92; P=0.0005), though this protective effect was absent in Han Chinese.
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