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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study

Bonomi, A (author)
IRCCS, Ctr Cardiol Monzino, Milan, Italy
Veglia, F (author)
IRCCS, Ctr Cardiol Monzino, Milan, Italy
Baldassarre, D (author)
IRCCS, Ctr Cardiol Monzino, Milan, Italy; Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy
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Strawbridge, RJ (author)
Karolinska Institutet,Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland; Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden
Golabkesh, Z (author)
Karolinska Institutet,Karolinska Inst, Inst Environm Med, Unit Translat Epidemiol, Stockholm, Sweden
Sennblad, Bengt (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab
Leander, K (author)
Karolinska Institutet,Karolinska Inst, IMM, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden
Smit, AJ (author)
Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands; Univ Groningen, Groningen, Netherlands
Giral, P (author)
Grp Hosp Pitie Salpetriere, AP HP, Unites Prevent Cardiovasc, Serv Endocrinol Metab, Paris, France
Humphries, SE (author)
UCL, Ctr Cardiovasc Genet, London, England
Tremoli, E (author)
IRCCS, Ctr Cardiol Monzino, Milan, Italy
Hamsten, A (author)
Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden
de Faire, U (author)
Karolinska Institutet,Karolinska Inst, IMM, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden
Gigante, B (author)
Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden
Sirtori, CR (author)
Castelnuovo, S (author)
Calabresi, L (author)
Amato, M (author)
Frigerio, B (author)
Ravani, A (author)
Sansaro, D (author)
Coggi, D (author)
Tedesco, CC (author)
Eriksson, P (author)
Karolinska Institutet
Silveira, A (author)
Karolinska Institutet
Laguzzi, F (author)
Karolinska Institutet
Cooper, J (author)
Acharya, J (author)
Huttunen, K (author)
Rauramaa, E (author)
Pekkarinen, H (author)
Penttila, IM (author)
Torronen, J (author)
Rauramaa, R (author)
Van Gessel, AI (author)
Van Roon, AM (author)
Teune, GC (author)
Kuipers, WD (author)
Bruin, M (author)
Nicolai, A (author)
Haarsma-Jorritsma, P (author)
Mulder, DJ (author)
Bilo, HJG (author)
Smeets, GH (author)
Beaudeux, JL (author)
Kahn, JF (author)
Carreau, V (author)
Kontush, A (author)
Karppi, J (author)
Nurmi, T (author)
Nyyssonen, K (author)
Salonen, R (author)
Tuomainen, TP (author)
Tuomainen, J (author)
Kauhanen, J (author)
Kurl, S (author)
Vaudo, G (author)
Alaeddin, A (author)
Siepi, D (author)
Lupattelli, G (author)
Mannarino, E (author)
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 (creator_code:org_t)
2020-01-14
2020
English.
In: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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–maxβ = −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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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