Genotype at the -174G/C polymorphism of the interleukin-6 gene is associated with common carotid artery intimal-medial thickness: family study and meta-analysis.
OBJECTIVE
Studies in unrelated individuals have produced conflicting findings concerning the putative association between the interleukin-6 (IL-6) -174G/C polymorphism and carotid intimal-medial thickness (IMT). We have used a family-based genetic association design to assess the heritability of carotid IMT and to investigate the hypothesized association of carotid IMT with the IL-6 to -174G/C polymorphism.


METHODS
We studied 854 members of 224 white British families. The heritability of carotid IMT was determined using Multipoint Engine for Rapid Likelihood Inference. Genetic association analyses were carried out using ANOVA and family-based tests of association implemented in Quantitative Transmission Disequilibrium Test. A meta-analysis of previous studies of the association was conducted to place our result in context.


RESULTS
The heritability of carotid IMT was 24%. Under a recessive model (GG+GC versus CC), there was significant evidence of association between IL-6 to the -174G/C genotype and adjusted log(e) maximal carotid IMT (F=5.469; P=0.02). Family-based analyses using Quantitative Transmission Disequilibrium Test showed no evidence of population stratification as a cause of the observed association (chi2(1)=0.469; P=0.4934). The CC genotype was associated with a 4.8% increase in maximal carotid IMT and accounted for 0.6% of the observed variation in the trait, which is equivalent to 2.5% of the heritable component. A meta-analysis of the present and 2 previous large studies, which enrolled a total of 2930 subjects, confirmed the recessive effect of the C allele on carotid IMT (P=0.0014).


CONCLUSIONS
The genotype at the IL-6 to -174G/C polymorphism is associated with common carotid artery IMT, although the size of the genetic effect is small.
Mayosi
Bongani M
BM
Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom. bmayosi@uctgsh1.uct.ac.za
Avery
Peter J
PJ
Baker
Michelle
M
Gaukrodger
Nicole
N
Imrie
Helen
H
Green
Fiona R
FR
Farrall
Martin
M
Watkins
Hugh
H
Keavney
Bernard
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000704:Analysis of Variance; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000235:genetics*; D004452:Echocardiography; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D011110:Polymorphism, Genetic; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology*; D014463:Ultrasonography
D015850:Interleukin-6