Copy Number Variation of the Lipoprotein(a) (LPA) Gene is Associated with Coronary Artery Disease in a Southern Han Chinese Population

Overview

Journal Int J Clin Exp Med

Specialty General Medicine

Date 2014 Nov 25

PMID 25419416

Citations 10

Authors

Zhijun Wu

Haihui Sheng

Yanjia Chen

Jing Tang

Yan Liu

Qiujing Chen

Lin Lu

Wei Jin

Affiliations

Soon will be listed here.

Abstract

Copy number variations (CNVs), genomic duplication or deletion events occurring at larger than 1 kb scale, contribute to the complex diseases substantially. Lipoprotein(a) [Lp(a)] is a major inherited risk factor for atherosclerosis and coronary artery disease (CAD). We investigated the association between a CNV of the Lp(a) (LPA) gene and CAD. The case-control study included 271 CAD patients and 207 controls diagnosed by coronary angiography. A taqman real-time fluorescence PCR based technique was developed according to the 2 × 2(-ΔΔCt±SD) calculation method. We detected LPA CNVs with a range of 1, 2 and 3. The 1 copy number carriers had a significantly reduced risk of CAD compared with those with 2 copy number after adjusting for the confounding factors (P < 0.001, OR = 0.38, 95% CI 0.23-0.64). Further stratified analyses suggested a significant protective effect of the 1 copy number in the elderly population (P = 0.008), females (P = 0.007) as well as in populations with non-hyperlipidemia (P = 0.003), hypertension (P = 0.001), non-smoking (P < 0.001) and high Lp(a) (≥ 0.3 g/L) levels (P = 0.001). The 1 copy number of the LPA gene may be an independent protective factor of CAD in a southern Han Chinese population, particularly in females and the elderly.

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References

Adams Jr H, Bendixen B, Kappelle L, Biller J, Love B, Gordon D . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24(1):35-41. DOI: 10.1161/01.str.24.1.35. View

Parson W, Kraft H, Niederstatter H, Lingenhel A, Kochl S, Fresser F . A common nonsense mutation in the repetitive Kringle IV-2 domain of human apolipoprotein(a) results in a truncated protein and low plasma Lp(a). Hum Mutat. 2004; 24(6):474-80. DOI: 10.1002/humu.20101. View

Fanciulli M, Norsworthy P, Petretto E, Dong R, Harper L, Kamesh L . FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet. 2007; 39(6):721-3. PMC: 2742197. DOI: 10.1038/ng2046. View

Edelstein C, Pfaffinger D, Hinman J, Miller E, Lipkind G, Tsimikas S . Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein(a). J Biol Chem. 2003; 278(52):52841-7. DOI: 10.1074/jbc.M310425200. View

Ohira T, Schreiner P, Morrisett J, Chambless L, Rosamond W, Folsom A . Lipoprotein(a) and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2006; 37(6):1407-12. DOI: 10.1161/01.STR.0000222666.21482.b6. View

Trommsdorff M, Kochl S, Lingenhel A, Kronenberg F, Delport R, Vermaak H . A pentanucleotide repeat polymorphism in the 5' control region of the apolipoprotein(a) gene is associated with lipoprotein(a) plasma concentrations in Caucasians. J Clin Invest. 1995; 96(1):150-7. PMC: 185183. DOI: 10.1172/JCI118015. View

Topol E . Simon Dack Lecture. The genomic basis of myocardial infarction. J Am Coll Cardiol. 2005; 46(8):1456-65. DOI: 10.1016/j.jacc.2005.06.064. View

Tregouet D, Konig I, Erdmann J, Munteanu A, Braund P, Hall A . Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat Genet. 2009; 41(3):283-5. DOI: 10.1038/ng.314. View

Silaste M, Rantala M, Alfthan G, Aro A, Witztum J, Kesaniemi Y . Changes in dietary fat intake alter plasma levels of oxidized low-density lipoprotein and lipoprotein(a). Arterioscler Thromb Vasc Biol. 2004; 24(3):498-503. DOI: 10.1161/01.ATV.0000118012.64932.f4. View

10.

Cantin B, Gagnon F, Moorjani S, Despres J, Lamarche B, Lupien P . Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J Am Coll Cardiol. 1998; 31(3):519-25. DOI: 10.1016/s0735-1097(97)00528-7. View

11.

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

12.

Wu Z, Lou Y, Jin W, Liu Y, Lu L, Chen Q . The Connexin37 gene C1019T polymorphism and risk of coronary artery disease: a meta-analysis. Arch Med Res. 2013; 45(1):21-30. DOI: 10.1016/j.arcmed.2013.12.001. View

13.

Sun L, Li Z, Zhang H, Ma A, Liao Y, Wang D . Pentanucleotide TTTTA repeat polymorphism of apolipoprotein(a) gene and plasma lipoprotein(a) are associated with ischemic and hemorrhagic stroke in Chinese: a multicenter case-control study in China. Stroke. 2003; 34(7):1617-22. DOI: 10.1161/01.STR.0000078370.12085.02. View

14.

Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G . The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science. 2005; 307(5714):1434-40. DOI: 10.1126/science.1101160. View

15.

Wu Z, Lou Y, Jin W, Liu Y, Lu L, Lu G . The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2) is associated with increased risk of coronary artery disease: a meta-analysis. PLoS One. 2013; 7(12):e53105. PMC: 3534032. DOI: 10.1371/journal.pone.0053105. View

16.

Wong C, Christen T, Kwak B . Connexins in leukocytes: shuttling messages?. Cardiovasc Res. 2004; 62(2):357-67. DOI: 10.1016/j.cardiores.2003.12.015. View

17.

Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P . Large-scale copy number polymorphism in the human genome. Science. 2004; 305(5683):525-8. DOI: 10.1126/science.1098918. View

18.

Topol E, Smith J, Plow E, Wang Q . Genetic susceptibility to myocardial infarction and coronary artery disease. Hum Mol Genet. 2006; 15 Spec No 2:R117-23. DOI: 10.1093/hmg/ddl183. View

19.

Wu Z, Lou Y, Jin W, Liu Y, Lu L, Chen Q . Relationship of the p22phox (CYBA) gene polymorphism C242T with risk of coronary artery disease: a meta-analysis. PLoS One. 2013; 8(9):e70885. PMC: 3764124. DOI: 10.1371/journal.pone.0070885. View

20.

Sharp A, Locke D, McGrath S, Cheng Z, Bailey J, Vallente R . Segmental duplications and copy-number variation in the human genome. Am J Hum Genet. 2005; 77(1):78-88. PMC: 1226196. DOI: 10.1086/431652. View