An association study between genetic polymorphisms related to lipoprotein-associated phospholipase A2 and coronary heart disease

Xu,Limin; Zhou,Jianqing; Huang,Stephanie; Huang,Yi; Le,Yanping; Jiang,Danjie; Wang,Feiming; Yang,Xi; Xu,Weifeng; Huang,Xiaoyan; Dong,Changzheng; Zhang,Lina; Ye,Meng; Lian,Jiangfang; Duan,Shiwei

doi:10.3892/etm.2013.911

An association study between genetic polymorphisms related to lipoprotein-associated phospholipase A2 and coronary heart disease

Authors:
- Limin Xu
- Jianqing Zhou
- Stephanie Huang
- Yi Huang
- Yanping Le
- Danjie Jiang
- Feiming Wang
- Xi Yang
- Weifeng Xu
- Xiaoyan Huang
- Changzheng Dong
- Lina Zhang
- Meng Ye
- Jiangfang Lian
- Shiwei Duan
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Affiliations: School of Medicine, The Affiliated Hospital, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Ningbo Medical Center, Lihuili Hospital, Ningbo, Zhejiang 315041, P.R. China, Department of Medicine, University of Chicago, Chicago, IL 60637, USA, Zhejiang Zhenhai Middle School, Ningbo, Zhejiang 315200, P.R. China
Published online on: January 21, 2013 https://doi.org/10.3892/etm.2013.911
Pages: 742-750

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Abstract

Previous genome-wide association studies (GWAS) have revealed seven single nucleotide polymorphisms (SNPs) that affect lipoprotein-associated phospholipase A2 (Lp-PLA2) activity or levels in American and European individuals. A total of 290 coronary heart disease (CHD) patients, 198 non-CHD patients and 331 unrelated healthy volunteers were recruited for the present case-control study of Han Chinese. Four SNPs (rs964184 of ZNF259, rs7528419 of CELSR2 and rs7756935 and rs1805017 of PLA2G7) were shown to be significantly associated with CHD. The rs964184-G allele of the ZNF259 gene was identified as a risk factor of CHD in females (odds ratio (OR) =1.49, 95% confidence interval (CI) =1.00-2.22, P=0.05). The rs7528419-G allele of the CELSR2 gene was protective against CHD in males (OR=0.48, 95% CI=0.25‑0.93, P=0.04). The other two alleles (rs7756935-C and rs1805017-A) of the PLA2G7 gene acted as protective factors against CHD in females (rs7756935-C: OR=0.59, 95% CI=0.35-1.00, P=0.05; rs1805017-A: OR=0.51, 95% CI=0.28-0.93, P=0.03). Moreover, rs1805017 of the PLA2G7 gene was associated with the severity of CHD only in females (r2=0.02, P=0.04). We identified four Lp-PLA2-associated SNPs significantly associated with CHD in a Han Chinese population. Specifically, rs7528419 was protective factor against CHD in males, while the other two SNPs (rs7756935 and rs1805017 of the PLA2G7 gene) were protective factors against CHD in females and rs964184 of the ZNF259 gene was regarded as a risk factor for CHD in females.

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1.	Epps KC and Wilensky RL: Lp-PLA(2)- a novel risk factor for high-risk coronary and carotid artery disease. J Intern Med. 269:94–106. 2011. View Article : Google Scholar : PubMed/NCBI
2.	Rubinstein A and Izkhakov E: Lipoprotein associated phospholipase A2. Harefuah. 150:136–140. 2052011.(In Hebrew).
3.	Zheng GH, Chen HY, Xiong SQ and Chu JF: Lipoprotein-associated phospholipase A2 gene V279F polymorphisms and coronary heart disease: a meta-analysis. Mol Biol Rep. 38:4089–4099. 2011. View Article : Google Scholar : PubMed/NCBI
4.	Ballantyne CM, Hoogeveen RC, Bang H, et al: Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 109:837–842. 2004. View Article : Google Scholar
5.	Suchindran S, Rivedal D, Guyton JR, et al: Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet. 6:e10009282010. View Article : Google Scholar : PubMed/NCBI
6.	Sandhu MS, Waterworth DM, Debenham SL, et al: LDL-cholesterol concentrations: a genome-wide association study. Lancet. 371:483–491. 2008. View Article : Google Scholar : PubMed/NCBI
7.	Assmann G, Schulte H, von Eckardstein A and Huang Y: High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and patho-physiological implications for reverse cholesterol transport. Atherosclerosis. 124:S11–S20. 1996. View Article : Google Scholar
8.	Gordon T, Castelli WP, Hjortland MC, Kannel WB and Dawber TR: High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 62:707–714. 1977. View Article : Google Scholar : PubMed/NCBI
9.	Lim S, Park YM, Sakuma I and Koh KK: How to control residual cardiovascular risk despite statin treatment: Focusing on HDL-cholesterol. Int J Cardiol. April 12–2012.(Epub ahead of print).
10.	Sertic J, Skoric B, Lovric J, Bozina T and Reiner Z: Does Lp-PLA2 determination help predict atherosclerosis and cardiocerebrovascular disease? Acta Med Croatica. 64:237–245. 2010.(In Croatian).
11.	Thompson A, Gao P, Orfei L, et al: Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 375:1536–1544. 2010. View Article : Google Scholar
12.	Delgado P, Chacon P, Penalba A, et al: Lipoprotein-associated phospholipase A(2) activity is associated with large-artery atherosclerotic etiology and recurrent stroke in TIA patients. Cerebrovasc Dis. 33:150–158. 2012. View Article : Google Scholar : PubMed/NCBI
13.	Grallert H, Dupuis J, Bis JC, et al: Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies. Eur Heart J. 33:238–251. 2012. View Article : Google Scholar
14.	Higgs ZC, Macafee DA, Braithwaite BD and Maxwell-Armstrong CA: The Seldinger technique: 50 years on. Lancet. 366:1407–1409. 2005.PubMed/NCBI
15.	No authors listed:. Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation. 59:607–609. 1979. View Article : Google Scholar
16.	Gabriel S, Ziaugra L and Tabbaa D: SNP genotyping using the Sequenom MassARRAY iPLEX platform. Curr Protoc Hum Genet Chapter 2. Unit 2.12,. 2009. View Article : Google Scholar
17.	Excoffier L and Lischer HE: Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour. 10:564–567. 2010. View Article : Google Scholar : PubMed/NCBI
18.	Sham PC and Curtis D: Monte Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann Hum Genet. 59:97–105. 1995. View Article : Google Scholar : PubMed/NCBI
19.	Dupont WD and Plummer WD Jr: Power and sample size calculations. A review and computer program. Control Clin Trials. 11:116–128. 1990. View Article : Google Scholar : PubMed/NCBI
20.	Emslie C: Women, men and coronary heart disease: a review of the qualitative literature. J Adv Nurs. 51:382–395. 2005. View Article : Google Scholar : PubMed/NCBI
21.	Gorelick PB: Lipoprotein-associated phospholipase A2 and risk of stroke. Am J Cardiol. 101:34F–40F. 2008. View Article : Google Scholar : PubMed/NCBI
22.	Samani NJ, Braund PS, Erdmann J, et al: The novel genetic variant predisposing to coronary artery disease in the region of the PSRC1 and CELSR2 genes on chromosome 1 associates with serum cholesterol. J Mol Med (Berl). 86:1233–1241. 2008. View Article : Google Scholar : PubMed/NCBI
23.	Zhou L, Ding H, Zhang X, et al: Genetic variants at newly identified lipid loci are associated with coronary heart disease in a Chinese Han population. PLoS One. 6:e274812011. View Article : Google Scholar : PubMed/NCBI
24.	Casas JP, Ninio E, Panayiotou A, et al: PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry. Circulation. 121:2284–2293. 2010. View Article : Google Scholar
25.	Sutton BS, Crosslin DR, Shah SH, et al: Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets. Hum Mol Genet. 17:1318–1328. 2008. View Article : Google Scholar : PubMed/NCBI
26.	Li L, Qi L, Lv N, et al: Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population. Ann Hum Genet. 75:605–611. 2011. View Article : Google Scholar : PubMed/NCBI
27.	Jang Y, Kim OY, Koh SJ, et al: The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men. J Clin Endocrinol Metab. 91:3521–3527. 2006. View Article : Google Scholar : PubMed/NCBI
28.	Jang Y, Waterworth D, Lee JE, et al: Carriage of the V279F null allele within the gene encoding Lp-PLA(2) is protective from coronary artery disease in South Korean males. PLoS One. 6:e182082011. View Article : Google Scholar : PubMed/NCBI
29.	Willer CJ, Sanna S, Jackson AU, et al: Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 40:161–169. 2008. View Article : Google Scholar : PubMed/NCBI
30.	Naj AC, West M, Rich SS, et al: Association of scavenger receptor class B type I polymorphisms with subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Genet. 3:47–52. 2010. View Article : Google Scholar : PubMed/NCBI
31.	Brautbar A, Covarrubias D, Belmont J, et al: Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia. Atherosclerosis. 219:737–742. 2011. View Article : Google Scholar
32.	Waterworth DM, Ricketts SL, Song K, et al: Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arterioscler Thromb Vasc Biol. 30:2264–2276. 2010. View Article : Google Scholar : PubMed/NCBI
33.	Guo L, Song Z, Li M, et al: Scavenger receptor BI protects against septic death through its role in modulating inflammatory response. J Biol Chem. 284:19826–19834. 2009. View Article : Google Scholar : PubMed/NCBI
34.	Rodriguez-Esparragon F, Rodriguez-Perez JC, Hernandez-Trujillo Y, et al: Allelic variants of the human scavenger receptor class B type 1 and paraoxonase 1 on coronary heart disease: genotype-phenotype correlations. Arterioscler Thromb Vasc Biol. 25:854–860. 2005. View Article : Google Scholar
35.	Papp AC, Pinsonneault JK, Wang D, et al: Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk. PLoS One. 7:e319302012. View Article : Google Scholar : PubMed/NCBI
36.	Schierer A, Been LF, Ralhan S, Wander GS, Aston CE and Sanghera DK: Genetic variation in cholesterol ester transfer protein, serum CETP activity, and coronary artery disease risk in Asian Indian diabetic cohort. Pharmacogenet Genomics. 22:95–104. 2012. View Article : Google Scholar : PubMed/NCBI
37.	Smith EN, Chen W, Kahonen M, et al: Longitudinal genome-wide association of cardiovascular disease risk factors in the Bogalusa heart study. PLoS Genet. 6:e10010942010. View Article : Google Scholar : PubMed/NCBI
38.	Borggreve SE, Hillege HL, Wolffenbuttel BH, et al: An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol: a population-based study. J Clin Endocrinol Metab. 91:3382–3388. 2006. View Article : Google Scholar
39.	Anand SS, Xie C, Pare G, et al: Genetic variants associated with myocardial infarction risk factors in over 8000 individuals from five ethnic groups: The INTERHEART Genetics Study. Circ Cardiovasc Genet. 2:16–25. 2009. View Article : Google Scholar : PubMed/NCBI
40.	Yang KC, Su YN, Shew JY, et al: LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population. J Formos Med Assoc. 106:799–807. 2007. View Article : Google Scholar : PubMed/NCBI
41.	Ahmed W, Ajmal M, Sadeque A, et al: Novel and recurrent LDLR gene mutations in Pakistani hypercholesterolemia patients. Mol Biol Rep. 39:7365–7372. 2012. View Article : Google Scholar : PubMed/NCBI
42.	Slimani A, Jelassi A, Jguirim I, et al: Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian familial hypercholesterolemia patients. Atherosclerosis. 222:158–166. 2012. View Article : Google Scholar : PubMed/NCBI