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Göteborgs universitets publikationer

Pharmacogenetic Determinants of Statin-Induced Reductions in C-Reactive Protein

Författare och institution:
A. Y. Chu (-); F. Guilianini (-); B. J. Barratt (-); Fredrik Nyberg (Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa); D. I. Chasman (-); P. M. Ridker (-)
Publicerad i:
Circulation-Cardiovascular Genetics, 5 ( 1 ) s. 58-65
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Background-In randomized trials, statins reduce plasma levels of C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDL-C), and the magnitude of event reduction relates to on-treatment levels of both. However, whether different mechanisms underlie statin-induced CRP and LDL-C reduction is unknown. Methods and Results-We performed a study to evaluate potential genetic determinants of CRP response using genome-wide genetic data from a total of 6766 participants of European ancestry randomly allocated to 20 mg/d of rosuvastatin or placebo in the JUPITER trial. Among 3386 rosuvastatin-allocated individuals, both CRP and LDL-C levels were reduced by 50% after 12 months of therapy (P<0.001 for both) and essentially uncorrelated (r(2)<0.03). No variants in the 3 genes (ABCG2, LPA, and APOE) that previously showed genome-wide association with LDL-C reduction in this cohort and none of the candidate single-nucleotide polymorphisms associated with LDL-C reduction were associated with rosuvastatin-induced CRP change after multiple testing correction. Among candidate single-nucleotide polymorphisms selected from prior genetic analyses of baseline CRP, CRP reduction was associated with rs2794520 in CRP (mean, -3.5% [SE, 2.0%] change in CRP per minor allele; P=6.4 x 10(-4)) and with rs2847281 in PTPN2 (mean, 3.7% [SE, 1.9%] change in CRP per minor allele; P=7.4 x 10(-4)). These associations remained significant after multiple testing correction but were not significant in a formal test of interaction. Neither variant was associated with rosuvastatin-induced LDL-C reduction or with CRP reduction among 3380 placebo-allocated JUPITER participants. Conclusions-The genetic determinants of rosuvastatin-induced CRP reduction differ from, and are largely independent of, the major pharmacogenetic determinants of rosuvastatin-induced LDL-C reduction. This supports the hypothesis that differing pathways may mediate the anti-inflammatory and lipid-lowering properties of statin therapy. (Circ Cardiovasc Genet. 2012;5:58-65.)
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Kardiologi ->
Kardiovaskulär medicin
C-reactive protein, cholesterol, genetics, inflammation, statins, genome-wide association, lipid-lowering response, cholesterol levels, coronary events, whole-genome, therapy, disease, gene, sequence, simvastatin
Postens nummer:
Posten skapad:
2012-11-26 11:07

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