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Supplementary Material for: Variants of <i>HSPA1A </i>in Combination with Plasma Hsp70 and Anti-Hsp70 Antibody Levels Associated with Higher Risk of Acute Coronary Syndrome

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<i>Objectives:</i> It was the aim of our study to investigate whether polymorphisms of <i>HSP70</i> have an affect on antigen and antibody levels in acute coronary syndrome (ACS) patients and normal controls, and the possible joint effect of variants and antigen and antibody levels on the risk of ACS. <i>Methods:</i> Three single nucleotide polymorphisms of <i>HSPA1A</i> and <i>HSPA1L</i> were evaluated in 520 ACS patients and 520 age- and sex-matched controls. Plasma extracellular Hsp70 (eHsp70) and anti-Hsp70 antibody levels were determined using ELISA. <i>Results:</i> Individuals with +190G/C (rs1043618) CC genotype in <i>HSPA1A</i> had higher levels of eHsp70 in controls and lower levels of anti-Hsp70 body in ACS, compared with +190G/C GG carriers. Significantly increased ACS risks of 2.93 and 3.53 fold were found in subjects with the +190G/C CC genotype and high eHsp70 levels or low anti-Hsp70 antibody levels, respectively. The highest risk of ACS was found in subjects with +190G/C CC genotypes, high eHsp70 and low anti-Hsp70 antibody levels compared with those in the reference group (OR = 7.57, 95% CI 3.04–18.87). <i>Conclusions:</i> The +190G/C polymorphism of <i>HSPA1A</i> may contribute to influence eHsp70 levels in controls and anti-Hsp70 antibody levels in ACS, and the +190G/C genotypes, eHsp70 and anti-Hsp70 antibody levels may have a joint effect on the risk of ACS.

研究目的:本研究旨在探讨热休克蛋白70(heat shock protein 70, HSP70)基因多态性对急性冠脉综合征(acute coronary syndrome, ACS)患者与正常对照人群的抗原、抗体水平的影响,以及基因变异与抗原、抗体水平联合对ACS发病风险的潜在作用。 研究方法:纳入520例ACS患者及520例年龄、性别匹配的正常对照者,对HSPA1A与HSPA1L基因的3个单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点进行基因分型;采用酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)检测血浆细胞外热休克蛋白70(extracellular heat shock protein 70, eHsp70)水平及抗Hsp70抗体水平。 研究结果:与+190G/C(rs1043618)GG基因型携带者相比,HSPA1A基因+190G/C CC基因型携带者在正常对照人群中eHsp70水平更高,而在ACS患者中抗Hsp70抗体水平更低。携带+190G/C CC基因型且eHsp70水平升高,或抗Hsp70抗体水平降低的受试者,其ACS发病风险分别显著升高2.93倍与3.53倍。与参考组相比,同时携带+190G/C CC基因型、eHsp70水平升高且抗Hsp70抗体水平降低的受试者,其ACS发病风险最高(优势比(odds ratio, OR)=7.57,95%置信区间(confidence interval, CI)3.04~18.87)。 研究结论:HSPA1A基因+190G/C多态性可能影响正常对照人群的eHsp70水平及ACS患者的抗Hsp70抗体水平,且该位点多态性、eHsp70与抗Hsp70抗体水平可能对ACS发病风险存在联合作用。

提供机构:
Karger Publishers
创建时间:
2017-06-20
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