Gambhir Jasvinder K, Kaur Harsimrut, Prabhu Krishna M, Morrisett Joel D, Gambhir Daljeet S
Department of Biochemistry, University College of Medical Sciences, Shahdara, Delhi-110095, India.
Clin Biochem. 2008 May;41(7-8):453-8. doi: 10.1016/j.clinbiochem.2008.01.016. Epub 2008 Feb 5.
The purpose of this study was to explore the association between lipoprotein (a) [Lp(a)] levels, apo(a) isoforms and family history of premature coronary artery disease (CAD) in young Asian Indians.
220 patients (age <40 years) with angiographic evidence of CAD and 160 age matched healthy controls were enrolled for the study. Thirty one percent of the patients and 17% of the controls had positive family history (PFH) of premature CAD. Plasma Lp(a) levels were determined by ELISA and apo(a) isoform size was determined using high-resolution immunoblotting method.
Median plasma Lp(a) levels were 2.5 times higher in patients as compared to controls (30 mg/dL vs 12.7 mg/dL; p<0.05). The patient group having a heterozygous apo(a) isoform pattern showed higher Lp(a) levels as compared to the homozygous group (44.0+/-38.7 vs 28.0+/-26.4 mg/dL; p<0.001). Further low molecular weight apo(a) isoforms (LMW; <22 KIV repeats) were prevalent among CAD patients with PFH as compared to negative family history (62% vs 14%, p<0.05) and this group had the highest Lp(a) levels. Stepwise regression analysis showed that Lp(a) levels and not the apo(a) isoform size, entered the model as significant independent predictors of CAD in young Asian Indians.
This study suggests that elevated Lp(a) levels confer genetic predisposition to CAD in young Asian Indians. Thus determination of Lp(a) levels along with other risk factors should be used to assess overall risk for CAD in this ethnic group.
本研究旨在探讨年轻亚洲印度人脂蛋白(a)[Lp(a)]水平、载脂蛋白(a)[apo(a)]异构体与早发冠心病(CAD)家族史之间的关联。
本研究纳入了220例年龄<40岁且有CAD血管造影证据的患者以及160例年龄匹配的健康对照。31%的患者和17%的对照有早发CAD的阳性家族史(PFH)。采用酶联免疫吸附测定法(ELISA)测定血浆Lp(a)水平,使用高分辨率免疫印迹法测定apo(a)异构体大小。
患者的血浆Lp(a)水平中位数比对照高2.5倍(30 mg/dL对12.7 mg/dL;p<0.05)。与纯合子组相比,具有杂合子apo(a)异构体模式的患者组Lp(a)水平更高(44.0±38.7对28.0±26.4 mg/dL;p<0.001)。此外,与无家族史相比,低分子量apo(a)异构体(LMW;<22个KIV重复序列)在有PFH的CAD患者中更为普遍(62%对14%,p<0.05),且该组Lp(a)水平最高。逐步回归分析显示,在年轻亚洲印度人中,进入模型作为CAD显著独立预测因子的是Lp(a)水平而非apo(a)异构体大小。
本研究表明,Lp(a)水平升高使年轻亚洲印度人具有CAD的遗传易感性。因此,应结合其他危险因素测定Lp(a)水平,以评估该种族CAD的总体风险。