Shuvalova Yulia A, Khasanova Zukhra B, Kaminnaya Violetta I, Samoilova Elena V, Korotaeva Alexandra A, Rubanovich Alexander V, Kaminnyi Alexander I
Russian Cardiology Research and Production Complex, Department of Atherosclerosis Problems, 3rd Cherepkovskaya str, 15a, Moscow 121552, Russia.
Russian Cardiology Research and Production Complex, Laboratory of Medical Genetics, 3rd Cherepkovskaya str, 15a, Moscow 121552, Russia.
Gene. 2015 Jun 10;564(1):29-34. doi: 10.1016/j.gene.2015.03.030. Epub 2015 Mar 17.
Single nucleotide polymorphisms (SNPs) of the secretory phospholipase A2 type IIa (sPLA-IIa) gene (PLA2G2A) affect sPLA2-IIa level and activity in patients with diabetes mellitus, acute coronary syndrome or recent cardiovascular surgical interventions. Our study examined the effects of PLA2G2A SNPs on sPLA2-IIa levels and activity in patients with stable CHD.
The study included a total of 396 patients (30% women). Six SNPs of PLA2G2A: rs1774131, rs11573156, rs3753827, rs2236771, rs876018, and rs3767221, sPLA2-IIa level and activity were determined for all patients. Four SNPs (rs1774131, rs11573156, rs3753827, rs3767221) correlated with sPLA2-IIa level but not activity with the strongest correlation observed for rs11573156 (r=0.49, p=3.7·10(-13)). All partial correlations controlling for rs11573156 became insignificant, whereas, the partial correlation of rs11573156 with sPLA2-IIa level controlling for other SNPs remained significant. Only rs11573156 showed association with sPLA2-IIa level in multiple regression analysis. Haplotype CGGGTT was associated with a significantly higher sPLA2-IIa level but not activity compared with all other haplotypes after adjustment for gender, age, diabetes mellitus and statin use (p=0.0023).
According to our results the examined SNPs affect the sPLA2-IIa level to a greater extent than its activity in patients with stable CHD. It seems that, the impact of these SNPs on sPLA2-IIa level is caused by their linkage to rs11573156 whose minor alleles were associated with higher sPLA2-IIa level. At the same time haplotype CGGGTT, which includes the minor allele of rs11573156, was the dominant haplotype and was associated with the highest sPLA2-IIa level.
分泌型磷脂酶A2-IIa（sPLA-IIa）基因（PLA2G2A）的单核苷酸多态性（SNP）会影响糖尿病、急性冠状动脉综合征或近期接受心血管外科手术的患者的sPLA2-IIa水平和活性。我们的研究检测了PLA2G2A SNP对稳定型冠心病患者sPLA2-IIa水平和活性的影响。
该研究共纳入396例患者（30%为女性）。对所有患者测定了PLA2G2A的6个SNP：rs1774131、rs11573156、rs3753827、rs2236771、rs876018和rs3767221，以及sPLA2-IIa水平和活性。4个SNP（rs1774131、rs11573156、rs3753827、rs3767221）与sPLA2-IIa水平相关，但与活性无关，其中rs11573156的相关性最强（r=0.49，p=3.7×10⁻¹³）。所有控制rs11573156后的偏相关性均无统计学意义，而rs11573156在控制其他SNP后的sPLA2-IIa水平偏相关性仍有统计学意义。在多元回归分析中，只有rs11573156与sPLA2-IIa水平相关。在对性别、年龄、糖尿病和他汀类药物使用进行校正后，单倍型CGGGTT与所有其他单倍型相比，sPLA2-IIa水平显著更高，但与活性无关（p=0.0023）。
根据我们的结果，在稳定型冠心病患者中，所检测的SNP对sPLA2-IIa水平的影响大于对其活性的影响。这些SNP对sPLA2-IIa水平的影响似乎是由于它们与rs11573156的连锁，其次要等位基因与较高的sPLA2-IIa水平相关。同时，包含rs11573156次要等位基因的单倍型CGGGTT是主要单倍型，且与最高的sPLA2-IIa水平相关
