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Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study

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Abstract

The human PLA2G7 gene encodes lipoprotein-associated phospholipase A2 (Lp-PLA2), an emerging risk factor for cardiovascular diseases. In the present study, seven single nucleotide polymorphisms (SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease (CHD), of which 512 were patients with myocardial infarction (MI), and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA2 activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients, including 423 MI patients. Lp-PLA2 activity in CHD and MI cases was significantly higher (233.42 ± 57.66 and 234.27 ± 59.51 nmol ml−1 min−1, respectively) than in controls (211.47 ± 58.61 nmol ml−1 min−1). After adjusting for traditional risk factors by logistic regression, the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA2 activity were 1.27 (95% CI, 1.07–1.50) and 1.27 (95% CI, 1.05–1.54), respectively. Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA2 activity, but neither was associated with increased CHD risk. Both univariate and multivariate analyses, adjusting effects of conventional factors, indicated that the rs13210554 T allele increased the risk of MI in this Chinese Han population. In summary, an independent association of increased plasma Lp-PLA2 activity with CHD and MI existed in this Chinese Han Population. Although V279F and I198T mutations significantly decreased the activity of Lp-PLA2, only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA2 activity appears to influence the CHD and MI risk in Chinese Han population.

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Acknowledgments

This work was supported by the Ministry of Science and Technology of The People’s Republic of China (Grant No. 2006AA02A406) and by National Basic Research Program of China (Grant No. 2006CB503805). This study was also funded by a contractual agreement between Cardiovascular Institute and Fu Wai Hospital Beijing, China and GlaxoSmithKline Inc, New York, USA. Several researchers employed by GlaxoSmithKline Inc were members of the Study Steering Committee that designed the study. However, the study was conducted, analyzed, and interpreted by the investigators independently of the sponsor.

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Authors and Affiliations

  1. Department of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, 100037, Beijing, China

    Liping Hou, Shufeng Chen, Hongjiang Yu, Xiangfeng Lu, Jianhong Chen, Laiyuan Wang, Jianfeng Huang & Dongfeng Gu

  2. National Human Genome Center at Beijing, Beijing, China

    Liping Hou & Dongfeng Gu

  3. Peking Union Hospital, Beijing, China

    Zhongjie Fan

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  1. Liping Hou
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  2. Shufeng Chen
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Correspondence to Dongfeng Gu.

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439_2008_587_MOESM1_ESM.doc

Supplementary Figure 1 Pair-wise LD among seven SNPs in the CHD group. The numbers inside the squares are D′×100 (DOC 117 kb)

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Hou, L., Chen, S., Yu, H. et al. Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study. Hum Genet 125, 11–20 (2009). https://doi.org/10.1007/s00439-008-0587-4

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  • DOI: https://doi.org/10.1007/s00439-008-0587-4

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