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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study.
Genes and Immunity ( IF 5.0 ) Pub Date : 2020-01-14 , DOI: 10.1038/s41435-019-0090-z
Alice Bonomi 1 , Fabrizio Veglia 1 , Damiano Baldassarre 1, 2 , Rona J Strawbridge 3, 4 , Zahra Golabkesh 5 , Bengt Sennblad 6 , Karin Leander 7 , Andries J Smit 8 , Philippe Giral 9 , Steve E Humphries 10 , Elena Tremoli 1 , Anders Hamsten 4 , Ulf de Faire 7 , Bruna Gigante 4 ,
Affiliation  

The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10-5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10-5) and inversely associated with c-IMT (c-IMTmean-max β = -0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.

中文翻译:

与sgp130循环水平相关的遗传变异分析。IMPROVE研究的结果。

调节可溶性gp130(sgp130),白介素6驱动的动脉粥样硬化炎症反应拮抗剂的循环水平的基因在很大程度上是未知的。本研究的目的是鉴定与循环sgp130相关的遗传基因座,并探索与sgp130相关的变异体与亚临床动脉粥样硬化标记物之间的潜在关联。这项研究基于IMPROVE(n = 3703),这是一项旨在研究颈动脉内膜中层厚度决定因素的心血管多中心研究,该测量指标是亚临床动脉粥样硬化的一种度量。通过CardioMetaboChip和ImmunoChip对基因组DNA进行基因分型。使用通过PLINK v1.07调整了年龄,性别和人群分层的线性回归,测试了约360,842个SNP与经对数转换的sgp130的关联。选择1×10-5的p值作为显着性值的阈值。在探索性分析中,测试了与sgp130相关的SNP与c-IMT措施的相关性。我们确定了两个与sgp130水平显着相关的SNP,还有24个与sgp130水平相关的暗示性SNP。第14号染色体上的一个SNP(rs17688225)与sgp130血清水平呈正相关(β= 0.03 SE = 0.007,p = 4.77×10-5),与c-IMT呈负相关(c-IMTmean-maxβ= -0.001 SE = 0.005,p = 0.0342)。我们的数据表明,多个基因座可调节sgp130的水平,并暗示sgp130和c-IMT措施之间可能存在共同的途径。我们确定了两个与sgp130水平显着相关的SNP,还有24个与sgp130水平相关的暗示性SNP。第14号染色体上的一个SNP(rs17688225)与sgp130血清水平呈正相关(β= 0.03 SE = 0.007,p = 4.77×10-5),与c-IMT呈负相关(c-IMTmean-maxβ= -0.001 SE = 0.005,p = 0.0342)。我们的数据表明,多个基因座可调节sgp130的水平,并暗示sgp130和c-IMT措施之间可能存在共同的途径。我们确定了两个与sgp130水平显着相关的SNP,还有24个与sgp130水平相关的暗示性SNP。第14号染色体上的一个SNP(rs17688225)与sgp130血清水平呈正相关(β= 0.03 SE = 0.007,p = 4.77×10-5),与c-IMT呈负相关(c-IMTmean-maxβ= -0.001 SE = 0.005,p = 0.0342)。我们的数据表明,多个基因座可调节sgp130的水平,并暗示sgp130和c-IMT措施之间可能存在共同的途径。
更新日期:2020-01-14
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