Association of Inflammatory Gene Polymorphisms and Conventional Risk Factors With Arterial Stiffness by Age

Abstract

BackgroundInflammatory gene polymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory gene polymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness.MethodsWe recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene polymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP-1, ICAM-1, and TNF-α. Associations of CAVI with genetic and conventional risk factors were estimated by sex and age group (34–49, 50–59, and 60–69 years) using a general linear model. The association with 5-year change in CAVI was examined longitudinally.ResultsGlucose intolerance was associated with high CAVI among women in all age groups, while hypertension was associated with high CAVI among participants in all age groups, except younger women. Mean CAVI for the CD14 CC genotype was lower than those for the TT and CT genotypes (P for trend = 0.005), while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49 years (P = 0.006). No association of the other 6 polymorphisms with CAVI was observed. No association with 5-year change in CAVI was apparent.ConclusionsInflammatory gene polymorphisms were not associated with arterial stiffness. To confirm these results, further large-scale prospective studies are warranted.

Interactions between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases among the Japanese population

“…This study was conducted as a part of the Japan Multi-institutional Collaborative Cohort (J-MICC) study, which has been described elsewhere. 17 , 18 , 19 We conducted baseline surveys in five Amami island regions from 2005 to 2008 and three mainland regions in 2012. The subjects were individuals undergoing health-checkups that were conducted by the local government or private companies, and those aged 32–78 years were asked to participate in the study by filling informed consents (response rate: 69.8%).…”

Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases

“…Associations between inflammatory gene polymorphism and cardio-ankle vascular index were found only for the cluster of differentiation 14 (CD14) polymorphism among men aged 34–49 years in a study examining polymorphisms in several inflammatory genes ( 87 ). CD14 acts as a trigger in the production of cytokines ( 87 ).…”

Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk?

“…Interestingly, a small‐scale genetic study in middle‐aged Japanese men reported an association between arterial stiffness and a gene polymorphism in CD14, a receptor which co‐signals with TLR4 leading to an increase in inflammation (Kheradmand et al . ). In agreement, increased arterial stiffness has been reported in patients with chronic inflammatory diseases such as rheumatoid arthritis (Maki‐Petaja et al .…”

“…Genetic deletion of cardiotrophin 1, a member of the IL-6 cytokine family, leads to decreased arterial stiffness and collagen deposition in aged mice, via mechanisms linked to the down-regulation of inflammation (Lopez-Andres et al 2013). Interestingly, a small-scale genetic study in middle-aged Japanese men reported an association between arterial stiffness and a gene polymorphism in CD14, a receptor which co-signals with TLR4 leading to an increase in inflammation (Kheradmand et al 2013). In agreement, increased arterial stiffness has been reported in patients with chronic inflammatory diseases such as rheumatoid arthritis (Maki-Petaja et al 2006;Protogerou et al 2011) and inflammatory bowel disease (Zanoli et al 2012), consistent with the hypothesis that inflammation could play an important role in arterial stiffness pathogenesis, as it does in atherosclerosis (Fan et al 2014).…”