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全基因组关联研究鉴定出与白细胞介素 18 水平相关的 IL18-BCO2 基因座的变异。

Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels.

机构信息

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.

出版信息

Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):885-90. doi: 10.1161/ATVBAHA.109.199422. Epub 2010 Feb 11.

DOI:10.1161/ATVBAHA.109.199422
PMID:20150558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2841960/
Abstract

OBJECTIVE

Interleukin-18 (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.

METHODS AND RESULTS

We performed a 2-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 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1 x 10(-5) significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31 x 10(-8)). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5 x 10(-8)). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels.

CONCLUSIONS

This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

摘要

目的

白细胞介素-18（IL-18）是一种促炎细胞因子，参与先天和获得性免疫过程，与心血管疾病和 2 型糖尿病有关。我们试图确定与 IL-18 水平相关的常见遗传变异。

方法和结果

我们在欧洲血统的护士健康研究（NHS）和妇女基因组健康研究（WGHS）的女性中进行了 2 阶段全基因组关联研究。通过 ELISA 测量 IL-18 水平。在发现阶段（NHS，n=1523），IL18-BCO2 基因座的 7 个单核苷酸多态性（SNP）在 1 x 10（-5）的显著水平与 IL-18 浓度相关。BCO2 基因中的 SNP rs2115763 与 SNP rs2115763 相关性最强（P=6.31 x 10（-8））。在 WGHS（435 名女性）的模拟复制证实了这些发现。两项研究的综合分析表明，SNP rs2115763、rs1834481 和 rs7106524 达到了全基因组显著水平（P<5 x 10（-8））。正向选择分析表明，SNP rs2115763 和 rs1834481 与 IL-18 水平独立相关（P=0.0002 和 0.0006）。这两个 SNP 共同解释了血浆 IL-18 水平变化的 2.9%。

结论

本研究在 IL18-BCO2 基因座鉴定了几个与 IL-18 水平相关的新变体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9031/2841960/5d42108d4b41/nihms181038f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9031/2841960/8dc07c65d6e4/nihms181038f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9031/2841960/5d42108d4b41/nihms181038f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9031/2841960/8dc07c65d6e4/nihms181038f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9031/2841960/5d42108d4b41/nihms181038f2.jpg

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