TY - JOUR
T1 - Genome-Wide Association Study of CRP Response to Statin Therapy in Diabetes in the CARDS Trial
AU - Colhoun, H.M.
AU - Deshmukh, H.A.
AU - Hitman, G.
AU - Livingstone, S.
AU - Durrington, P.N.
AU - Soedamah-Muthu, S.S.
N1 - http://diabetes.diabetesjournals.org/content/63/Supplement_1/A343.full.pdf#page=A424
PY - 2014
Y1 - 2014
N2 - Reduction of C reactive protein (CRP) may underlie part of the benefi ts
of statins in people with Type 2 diabetes (T2D), but whether this is through
different pathways than low-density lipoprotein cholesterol (LDL-C) reduction
is unclear. Our aim was to examine the variability in statin induced change in
CRP in diabetes and to seek genetic determinants of this change.
CRP was measured at baseline and one year in T2D patients in the CARDS
trial. ~2.5 million SNPs typed on Perlegen platform and imputed with HAPMAP
2 were used. Multivariate linear regression was used to model change from
baseline to 1 year in CRP in 1005 patients allocated to Atorvastatin. Posttreatment
(log)CRP level was used as the dependent variable with baseline
CRP, age, sex, BMI, smoking, duration of diabetes and HbA1c as covariates.
Genome-Complex Trait Analysis (GCTA) was used to identify narrow sense
heritability of CRP response.
The median (interquartile range) of change in CRP on statin was -0.12(-1.03,
0.69) mg/L with 45.3% of those on statin having no fall in CRP. In contrast
LDL-C fell in 96.5% of people on statin. Narrow-sense heritability h2(±SE) for
CRP response was 0.19(±0.24) compared to 0.05(±0.12) for LDL-C response.
Previously identifi ed variants for LDL-C -response to statin (in genes APOe2,
APOe4 and LPA) were not associated with CRP response (p>0.05) but three
borderline GWAS signifi cant loci (p
AB - Reduction of C reactive protein (CRP) may underlie part of the benefi ts
of statins in people with Type 2 diabetes (T2D), but whether this is through
different pathways than low-density lipoprotein cholesterol (LDL-C) reduction
is unclear. Our aim was to examine the variability in statin induced change in
CRP in diabetes and to seek genetic determinants of this change.
CRP was measured at baseline and one year in T2D patients in the CARDS
trial. ~2.5 million SNPs typed on Perlegen platform and imputed with HAPMAP
2 were used. Multivariate linear regression was used to model change from
baseline to 1 year in CRP in 1005 patients allocated to Atorvastatin. Posttreatment
(log)CRP level was used as the dependent variable with baseline
CRP, age, sex, BMI, smoking, duration of diabetes and HbA1c as covariates.
Genome-Complex Trait Analysis (GCTA) was used to identify narrow sense
heritability of CRP response.
The median (interquartile range) of change in CRP on statin was -0.12(-1.03,
0.69) mg/L with 45.3% of those on statin having no fall in CRP. In contrast
LDL-C fell in 96.5% of people on statin. Narrow-sense heritability h2(±SE) for
CRP response was 0.19(±0.24) compared to 0.05(±0.12) for LDL-C response.
Previously identifi ed variants for LDL-C -response to statin (in genes APOe2,
APOe4 and LPA) were not associated with CRP response (p>0.05) but three
borderline GWAS signifi cant loci (p
U2 - 10.2337/db14-1317-1629
DO - 10.2337/db14-1317-1629
M3 - Abstract
VL - 63
SP - A423-A423
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - S1
ER -