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

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.

A Replication Study and a Meta-Analysis of the Association between the CDKN2A rs1333049 Polymorphism and Coronary Heart Disease

“…We have previously evaluated several polymorphisms associated with the risk of CHD in Chinese [18][19][20][21] . The current study observed significant associations in both men and women, with women being more at risk (men: OR = 1.29, allele p = 0.01, women: OR = 1.64, allele p = 3.92E-04).…”

Positive association between PPARD rs2016520 polymorphism and coronary heart disease in a Han Chinese population

“…According to the criteria used in our previous studies (Zhou et al, 2012;Xu et al, 2013a), we divided the samples into 657 CHD cases and 640 non-CHD controls. All samples contained in this study were unrelated Han Chinese without congenital heart disease, cancer, or severe liver or kidney disease.…”

Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population

“…Despite recent advances in the understanding of PLA2G7, this variant on CHD is unclear and remains to be fully elucidated. Based on findings of Suchindran et al (2010) and Grallert et al (2012), we postulate that the point mutation in protein sequence can increase Lp-PLA2 mass and increase inflammatory responses in the vascular wall resulting in atherosclerosis (Liu et al 2014b;Xu et al 2013). Furthermore, the amino acid substation can influence the substrate affinities of PAF and thus leads to prolonged activities of this potent inflammatory protein (Kruse et al 2000).…”

“…Variants of Lp-PLA2 encoding gene (PLA2G7) predominantly contribute to the diversity of Lp-PLA2 activity or mass and CHD risk. PLA2G7 has been frequently studied and genetic association between the gene and CHD remains controversial (Xu et al 2013). Some studies, such as Li et al (2011) andZheng et al (2011), found a risk of CHD association with 279F.…”

“…For example, Sutton et al found that R92H was the most significantly associated SNP, while no difference was found between case group and control group with I198T mutations (Sutton et al 2008). Xu et al pointed out that R92H was protective factor against CHD in females (Xu et al 2013). Interestingly, the outcomes of studies conducted by Liu et al and Ninio et al turned out to be quite different (Liu et al 2006;Ninio et al 2004).…”