Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels.
Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels.
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DOI：
10.1161/atvbaha.109.199422
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
Qi L
中科院分区：
文献类型：
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作者：
He M;Cornelis MC;Kraft P;van Dam RM;Sun Q;Laurie CC;Mirel DB;Chasman DI;Ridker PM;Hunter DJ;Hu FB;Qi L
IL-18是一种促炎细胞因子，参与先天免疫和获得性免疫的过程，与心血管疾病和2型糖尿病相关。我们试图确定与IL-18水平相关的常见遗传变异。我们对护士健康研究(NHS)和女性基因组健康研究(WGHS)中的欧洲血统女性进行了两个阶段的全基因组关联研究。采用双抗体夹心ELISA法测定IL-18水平。在发现阶段(NHS，n=15 2 3)，IL 18-BCO2基因座上的7个SNP与IL-18浓度在1×10−5显著水平上相关。BCO2基因rs2115763单核苷酸多态与BCO2基因相关性最强(P值=6.31×10−8)。在WGHS的电子复制中(435名女性)证实了这些发现。两项研究的联合分析表明，rs2115763、rs1834481和rs7106524达到全基因组显著水平(P<；5×10−8)。前向选择分析显示rs2115763和rs1834481两个单核苷酸多态与IL-18水平独立相关(P分别为0.0002和0.0006)。这两个SNP共同解释了2.9%的血浆IL-18水平变化。这项研究确定了IL18-BCO2基因座上与IL-18水平相关的几个新的变异。
IL-18 is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. We performed a two-stage genome-wide association study among women of European ancestry from the Nurses’ Health Study (NHS) and Women’s Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n = 1523), 7 SNPs at IL18-BCO2 locus were associated with IL-18 concentrations at 1× 10−5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P value = 6.31× 10−8). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the two studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached genome-wide significance level (P < 5 ×10−8). Forward selection analysis indicated SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P = 0.0002 and 0.0006, respectively). The two SNPs together explained 2.9% of variation of plasma IL-18 levels. This study identified several novel variants at IL18-BCO2 locus associated with IL-18 levels.