Background

In recent years, lipoprotein (a) (Lp(a)) has been recognized as an important risk factor for cardiovascular disease (CVD). A variant in the LPA gene, rs10455872, has been associated with higher concentrations of Lp(a), as well as an increased risk of CVD in the general population.

Objective

The objective of the present study is to compare the predictive value of an LPA variant, rs10455872, as well as Lp(a) concentration on the prevalence of CVD and on the age of the first CVD event in a cohort of genetically confirmed heterozygous patients with familial hypercholesterolemia (FH).

Methods

Lp(a) total particle mass was measured by an enzyme-linked immunoassay kit. The rs10455872 genotype has been obtained via an exome chip genotyping method.

Results

The cohort comprised 88 carriers and 580 noncarriers of the rs10455872. The Lp(a) concentration (g/L) was significantly higher in carriers than in noncarriers (0.41 [0.33–0.60] vs 0.12 [0.05–0.27], respectively, P < .0001). There was a significant association between rs10455872 and prevalent CVD in a model corrected for classical CVD risk factors (odds ratio 1.97, 95% confidence interval 1.05–3.68, P = .04). There was a significant association between rs10455872 and the age of the first CVD event in a model corrected for all cardiovascular risk factors including Lp(a) levels (39.7 vs 43.9 years in carriers vs noncarriers, respectively, P = .02).

Conclusion

Our results suggest that the LPA variant rs10455872 is a good predictor of premature CVD risk in FH. This also suggest that targeting Lp(a) in FH subjects could be associated with further reduction in CVD risk.

中文翻译：

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LPA基因型与家族性高胆固醇血症的过早心血管疾病有关。

背景

近年来，脂蛋白（a）（Lp（a））被公认为是心血管疾病（CVD）的重要危险因素。LPA基因的一个变体rs10455872与更高浓度的Lp（a）相关联，并且与一般人群中发生CVD的风险增加有关。

客观的

本研究的目的是比较LPA变异体rs10455872的预测价值以及Lp（a）浓度对一组遗传学确诊的杂合子患者的CVD患病率和第一次CVD事件的年龄的预测价值。家族性高胆固醇血症（FH）。

方法

通过酶联免疫测定试剂盒测量Lp（a）的总颗粒质量。rs10455872基因型已通过外显子组芯片基因分型方法获得。

结果

该队列包含rs10455872的88个携带者和580个非携带者。携带者的Lp（a）浓度（g / L）显着高于非携带者（分别为0.41 [0.33-0.60]和0.12 [0.05-0.27]，P  <.0001）。在校正了经典CVD危险因素的模型中，rs10455872与流行CVD之间存在显着关联（赔率1.97，95％置信区间1.05-3.68，P  = .04）。在校正了所有心血管危险因素（包括Lp（a）水平）的模型中，rs10455872与第一次CVD事件的年龄之间存在显着相关性（携带者与非携带者分别为39.7和43.9年，P  = .02）。

结论

我们的结果表明，LPA变体rs10455872是FH中过早CVD风险的良好预测指标。这也表明在FH受试者中靶向Lp（a）可能与CVD风险的进一步降低有关。