| Autor: |
Bonomi A; Centro Cardiologico Monzino, IRCCS, Milan, Italy. alice.bonomi@ccfm.it., Veglia F; Centro Cardiologico Monzino, IRCCS, Milan, Italy., Baldassarre D; Centro Cardiologico Monzino, IRCCS, Milan, Italy.; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy., Strawbridge RJ; Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.; Department of Medicine Solna, Cardiovascular Medicine Unit, Karolinska Institutet, Stockholm, Sweden., Golabkesh Z; Unit of Translational Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden., Sennblad B; National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Leander K; Unit of Cardiovascular and Nutritional Epidemiology, IMM, Karolinska Institutet, Stockholm, Sweden., Smit AJ; Department of Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands., Giral P; Unités de Prévention Cardiovasculaire, Assistance Publique-Hôpitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Paris, France., Humphries SE; Centre for Cardiovascular Genetics, University College London, London, UK., Tremoli E; Centro Cardiologico Monzino, IRCCS, Milan, Italy., Hamsten A; Department of Medicine Solna, Cardiovascular Medicine Unit, Karolinska Institutet, Stockholm, Sweden., de Faire U; Unit of Cardiovascular and Nutritional Epidemiology, IMM, Karolinska Institutet, Stockholm, Sweden., Gigante B; Department of Medicine Solna, Cardiovascular Medicine Unit, Karolinska Institutet, Stockholm, Sweden. |
| Abstrakt: |
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-IMT mean-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. |
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