Genetic variation in LPAL2, LPA, and PLG predicts plasma lipoprotein(a) level and carotid artery disease risk.
Genetic variation in LPAL2, LPA, and PLG predicts plasma lipoprotein(a) level and carotid artery disease risk.
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DOI：
10.1161/strokeaha.110.591230
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发表时间：
2011-01
期刊：
影响因子：
8.3
通讯作者：
Jarvik GP
中科院分区：
文献类型：
--
作者：
Ronald J;Rajagopalan R;Cerrato F;Nord AS;Hatsukami T;Kohler T;Marcovina S;Heagerty P;Jarvik GP
脂蛋白（a）水平（Lp（a））是冠状动脉疾病的一个既定的危险因素，并与颈动脉疾病（CAAD）有关。LPA基因区域的遗传变异与CAAD风险之间的关系仍然未知。我们对530名严重CAAD患者和770名对照组的LPAL 2、LPA和PLG区域的单核苷酸多态性（SNP）进行基因分型，并对90名患者的Kringle IV 2型（KIV 2）重复长度进行基因分型。9个SNPs共同解释Lp（a）水平变异的30%。在考虑KIV 2拷贝数后，6个SNP与Lp（a）水平相关，其中显性KIV 2等位基因与这些标记组合可解释Lp（a）水平变异的60%。5个SNPs，包括rs10455872，每个次要等位基因的优势比为2.1，以及由rs10455872、rs6919346和rs3123629形成的单倍型是CAAD的显著预测因子。考虑Lp（a）水平后，LPA区域CAAD基因型相关的所有证据均被排除。LPA区域SNP捕获了KIV 2重复长度对Lp（a）水平的一些但不是全部影响。LPA区域SNP与CAAD之间存在关联，这似乎是由于对Lp（a）水平的影响。
Lipoprotein(a) level (Lp(a)) is an established risk factor for coronary artery disease and has been implicated in carotid artery disease (CAAD). The relationship between genetic variation in the LPA gene region and CAAD risk remains unknown. We genotyped single nucleotide polymorphisms (SNPs) in the LPAL2, LPA, and PLG region in 530 individuals with severe CAAD and 770 controls and kringle IV type 2 (KIV2) repeat length in a subset of 90 individuals. Nine SNPs collectively accounted for 30% of the variance in Lp(a) level. Six SNPs were associated with Lp(a) level after accounting for KIV2 copy number, and the dominant KIV2 allele combined with these markers explained 60% of the variance in Lp(a) level. Five SNPs, including rs10455872, which had an odds ratio of 2.1 per minor allele, and haplotypes formed by rs10455872, rs6919346, and rs3123629 were significant predictors of CAAD. After accounting for Lp(a) level, all evidence of CAAD-genotype association in the LPA region was eliminated. LPA region SNPs capture some but not all of the effect of KIV2 repeat length on Lp(a) level. There are associations between LPA region SNPs and CAAD which appear to be due to effects on Lp(a) level.