Polymorphism in the IL10 promoter region and early markers of atherosclerosis: the Cardiovascular Risk in Young Finns Study.
OBJECTIVE
Inflammatory factors modify the risk of coronary heart disease. Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene (IL10) is known to be associated with the variation of IL-10 production. We investigated whether single-base exchange polymorphisms -1082 G>A (rs1800896), -819 C>T (rs1800871) and -592 C>A (rs1800872) at IL10 gene are associated with risk factors and early markers of atherosclerosis in young subjects.


RESULTS
As a part of the Cardiovascular Risk in Young Finns Study, we determined carotid artery compliance (CAC), stiffness index (SI) and Young's elastic modulus (YEM), intima media thickness (IMT), IL10 genotype and atherosclerosis risk parameters for 2260 subjects aged 24-39 years. In male subjects CAC was lower in carriers of IL-10 high- to intermediate-producer haplotype -1082 G; -819 C; -592 C (GCC+, 1.96+/-0.67) than in noncarriers (GCC-, 2.10+/-0.62, %/10 mmHg, mean+/-SD, p=0.0010). An inverse association was observed in SI (GCC+, 5.76+/-2.12 and GCC-, 5.26+/-1.46, p=0.0034) and YEM (GCC+, 347+/-165 and GCC-, 305+/-110, mm Hg.mm, p=0.0005). Associations remained significant when adjusted to age, BMI, smoking and serum lipids as well as fasting glucose and insulin levels. The genetic effect size for these parameters was not significant in women.


CONCLUSIONS
IL10 promoter region high- to intermediate-producer haplotype GCC associates with decreased arterial elasticity in men. These results are in disconcordance with the supposed antiatheromatous properties of IL-10.
Heiskanen
Miikael
M
The Medical School at the University of Tampere, Finland.
Kähönen
Mika
M
Hurme
Mikko
M
Lehtimäki
Terho
T
Mononen
Nina
N
Juonala
Markus
M
Hutri-Kähönen
Nina
N
Viikari
Jorma
J
Raitakari
Olli
O
Hulkkonen
Janne
J
D000328:Adult; D050197:Atherosclerosis / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
D005819:Genetic Markers; D016753:Interleukin-10