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Associations of Common Genetic Variants on IL-17 Genes and Carotid Intima-Media Thickness.

ABSTRACT: AIM:Atherosclerosis is a chronic inflammatory process of the arterial wall and carotid intima-media thickness (cIMT) is regarded as its early marker. Several members of the IL-17 family are involved in pro-inflammatory functions. The specific aim of the study was to explore the relationships of common genetic variants on IL-17 genes with cIMT thickening. METHODS:In the discovery stage, 146 SNPs on 11 IL-17 genes were screened for their relationships with cIMT by a case-control study that enrolled 284 and 464 subjects who had thicker and normal cIMT, respectively. Findings were replicated by an independent case-control study that enrolled 282 subjects who had thicker cIMT and 282 age-sex-matched subjects who had normal cIMT. RESULTS:Among 134 eligible SNPs in the discovery study, only IL-17RC rs279545 was significantly correlated with cIMT (p=6.9×10-5). The rs279545 and 2 nearby linked SNPs rs55847610 and rs3846167 were included in the validation study. We found that the rs279545?G, rs55847610?G, and rs3846167?C were correlated with significantly higher likelihoods of having thicker cIMT. The corresponding multivariate-adjusted ORs were 1.462 (95% CI: 1.055-2.027), 1.481 (95% CI:1.090-2.013), and 1.589 (95% CI: 1.147-2.200), respectively. Analyses of rs279545-rs55847610 haplotypes showed that the multivariate-adjusted OR for A-A haplotype was significantly decreased (OR=0.665, 95% CI: 0.487-0.908) and for G-G haplotype was significantly increased (OR=1.539, 95% CI: 1.097-2.161). CONCLUSIONS:We first correlated cIMT, a preclinical clinical cardiovascular marker, with IL-17RC, the key molecule in the IL-17 signaling pathway. Our results indicated that IL-17RC may play critical role in the development of atherosclerotic diseases.

SUBMITTER: Wu TW

PROVIDER: S-EPMC6224208 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Associations of Common Genetic Variants on IL-17 Genes and Carotid Intima-Media Thickness.

Wu Tzu-Wei TW Chou Chao-Liang CL Chen Yi-Cheng YC Juang Yue-Li YL Wang Li-Yu LY

Journal of atherosclerosis and thrombosis 20180424 11

<h4>Aim</h4>Atherosclerosis is a chronic inflammatory process of the arterial wall and carotid intima-media thickness (cIMT) is regarded as its early marker. Several members of the IL-17 family are involved in pro-inflammatory functions. The specific aim of the study was to explore the relationships of common genetic variants on IL-17 genes with cIMT thickening.<h4>Methods</h4>In the discovery stage, 146 SNPs on 11 IL-17 genes were screened for their relationships with cIMT by a case-control stu ...[more]

PMID: 29695654

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Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Dataset Information

Associations of Common Genetic Variants on IL-17 Genes and Carotid Intima-Media Thickness.

Publications

Associations of Common Genetic Variants on IL-17 Genes and Carotid Intima-Media Thickness.

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