Heart and Vascular Research Institute, Harry Perkins Institute of Medical Research, Faculty of Health and Medical Sciences, Sir Charles Gairdner Hospital, University of Western Australia, Hospital Ave, Perth, Nedlands, WA, 6009, Australia.
Health Department of Western Australia, PathWest, Perth, Australia.
BMC Cardiovasc Disord. 2022 Mar 9;22(1):96. doi: 10.1186/s12872-022-02520-0.
It is unclear whether genetic variants identified from single nucleotide polymorphisms (SNPs) strongly associated with coronary heart disease (CHD) in genome-wide association studies (GWAS), or a genetic risk score (GRS) derived from them, can help stratify risk of recurrent events in patients with CHD.
Study subjects were enrolled at the close-out of the LIPID randomised controlled trial of pravastatin vs placebo. Entry to the trial had required a history of acute coronary syndrome 3-36 months previously, and patients were in the trial for a mean of 36 months. Patients who consented to a blood sample were genotyped with a custom designed array chip with SNPs chosen from known CHD-associated loci identified in previous GWAS. We evaluated outcomes in these patients over the following 10 years.
Over the 10-year follow-up of the cohort of 4932 patients, 1558 deaths, 898 cardiovascular deaths, 727 CHD deaths and 375 cancer deaths occurred. There were no significant associations between individual SNPs and outcomes before or after adjustment for confounding variables and for multiple testing. A previously validated 27 SNP GRS derived from SNPs with the strongest associations with CHD also did not show any independent association with recurrent major cardiovascular events.
Genetic variants based on individual single nucleotide polymorphisms strongly associated with coronary heart disease in genome wide association studies or an abbreviated genetic risk score derived from them did not help risk profiling in this well-characterised cohort with 10-year follow-up. Other approaches will be needed to incorporate genetic profiling into clinically relevant stratification of long-term risk of recurrent events in CHD patients.
目前尚不清楚全基因组关联研究（GWAS）中与冠心病（CHD）强烈相关的单核苷酸多态性（SNP）或由此衍生的遗传风险评分（GRS）是否有助于对 CHD 患者复发性事件的风险进行分层。
研究对象是 LIPID 随机对照普伐他汀与安慰剂试验结束时入选的患者。入选标准为 3-36 个月前发生急性冠状动脉综合征，且平均入组时间为 36 个月。同意采集血样的患者使用定制设计的芯片进行基因分型，芯片上的 SNP 选自先前 GWAS 中已确定的与 CHD 相关的基因座。我们评估了这些患者在接下来的 10 年内的结局。
在对 4932 例患者的队列进行 10 年随访期间，发生了 1558 例死亡、898 例心血管死亡、727 例 CHD 死亡和 375 例癌症死亡。在调整混杂因素和多重检验后，单个 SNP 与结局之间没有显著相关性，无论是在调整前还是调整后。先前验证过的 27 SNP GRS 来自与 CHD 最强相关的 SNP，也与复发性主要心血管事件没有任何独立关联。
基于与 GWAS 中与冠心病强烈相关的单个 SNP 或由此衍生的简化遗传风险评分的遗传变异，并不能帮助对该具有 10 年随访的特征明确的队列进行风险分层。需要其他方法将遗传分析纳入到 CHD 患者复发性事件长期风险的临床相关分层中。
