Journal of Lipid Research
Volume 60, Issue 8, August 2019, Pages 1440-1448
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Patient-Oriented and Epidemiological Research
A genome-wide association study on lipoprotein (a) levels and coronary artery disease severity in a Chinese population

https://doi.org/10.1194/jlr.P091009Get rights and content
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Lipoprotein (a) [Lp(a)] is a genetically determined risk factor of coronary artery disease (CAD). Previous genome-wide association studies (GWASs), which were mostly carried out in Caucasians, have identified many Lp(a)-associated SNPs. Here, we performed a GWAS on Lp(a) levels and further explored the relationships between Lp(a)-associated SNPs and CAD severity in 1,403 Han Chinese subjects. We observed that elevated Lp(a) levels were significantly associated with the increased synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) score and the counts of heavily calcified lesions and long-range lesions (LRLs; P < 0.05), which are defined as lesions spanning >20 mm. Moreover, we identified four independent SNPs, namely, rs7770628, rs73596816, and rs6926458 in LPA, and rs144217738 in SLC22A2, that were significantly associated with Lp(a) levels. We also found that rs7770628 was associated with high SYNTAX scores [odds ratio (OR) (95% CI): 1.37 (1.05–1.80), P = 0.0213, false discovery rate (FDR) = 0.0852], and that rs7770628 and rs73596816 were associated with high risk of harboring LRLs [OR (95% CI): 1.53 (1.17–2.01), P = 0.0018, FDR = 0.0072 and 1.72 (1.19–2.49), P = 0.0040, FDR = 0.0080, respectively]. Our study was a large-scale GWAS to identify Lp(a)-associated variants in the Han Chinese population. Our findings highlight the importance and potential of Lp(a) intervention and expand our understanding of CAD prevention and treatment.

single nucleotide polymorphism
SYNTAX score
genetics
lipid and lipoprotein metabolism
metabolic disease

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This study was supported by Ministry of Science and Technology of the People's Republic of China Grant 2017YFC0909301, National Natural Science Foundation of China Grants 81872934 and 81673514, and Key Research and Development Program of Guangdong Province Grant 2019B020229003.

The online version of this article (available at http://www.jlr.org) contains a supplement.

    Abbreviations:

    AST

    aspartate aminotransferase

    CAD

    coronary artery disease

    CAG

    coronary angiography

    CNV

    copy number variation

    CREA

    creatinine

    FDR

    false discovery rate

    GWAS

    genome-wide association study

    HCL

    heavily calcified lesion

    LD

    linkage disequilibrium

    LDLC

    LDL cholesterol

    LDLCc

    corrected LDL cholesterol

    Lp(a)

    lipoprotein (a)

    LRL

    long-range lesion

    MAF

    minor allele frequency

    OR

    odds ratio

    PCI

    percutaneous coronary intervention

    QC

    quality control

1

Y. Liu and H. Ma contributed equally to the study and are considered co-first authors.