Inflammation and endothelial function‐related gene polymorphisms are associated with carotid atherosclerosis—A study of community population in Southwest China

Abstract

Objectives To investigate the relationships between 18 single nucleotide polymorphisms with carotid atherosclerosis and whether interactions among these genes were associated with an increased risk of carotid atherosclerosis. Methods Face‐to‐face surveys were conducted with individuals aged 40 or older in eight communities. A total of 2377 individuals were included in the study. Ultrasound was used to detect carotid atherosclerosis in the included population. 18 loci of 10 genes associated with inflammation and endothelial function were detected. Gene‐gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Results Among the 2377 subjects, 445 (18.7%) subjects had increased intima‐media thickness in the common carotid artery (CCA‐IMT), and 398 (16.7%) subjects were detected with vulnerable plaque. In addition, NOS2A rs2297518 polymorphism was associated with increased CCA‐IMT, IL1A rs1609682, and HABP2 rs7923349 polymorphisms were associated with vulnerable plaque. Besides, GMDR analysis showed significant gene‐gene interactions among TNFSF4 rs1234313, IL1A rs1609682, TLR4 rs1927911, ITGA2 rs1991013, NOS2A rs2297518, IL6R rs4845625, ITGA2 rs4865756, HABP2 rs7923349, NOS2A rs8081248, HABP2 rs932650. Conclusion The prevalences of increased CCA‐IMT and vulnerable plaque were high in Southwestern China's high‐risk stroke population. Furthermore, inflammation and endothelial function‐related gene polymorphisms were associated with carotid atherosclerosis.

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population

“…For instance, Gardener et al (13) evaluated the associations between carotid plaque and 197 variants in 43 genes implicated in inflammation and endothelial function and demonstrated that the variants in 10 genes (IL6R, TNF, NOS2A, IL1A, TNFSF4, ITGA2, PPARA, TLR4, HABP2, and VCAM1) were associated with carotid plaque in the Northern Manhattan population. Similarly, our previous studies have also shown that specific single nucleotide polymorphisms (SNPs) in genes related to inflammation and endothelial function and high-risk interaction among HABP2 rs7923349, ITGA2 rs1991013, IL1A rs1609682, and NOS2A rs8081248, the interaction between ITGA2 rs4865756 and HABP2 rs7923349, and interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 were associated with carotid plaque vulnerability (10), carotid stenosis and IMT (14,15), and increased risk of carotid atherosclerosis (16), respectively. However, Gardener et al and our previous studies did not prospectively investigate the association of these variants and carotid atherosclerosis with subsequent stroke and other vascular events.…”

“…The community-based cross-sectional survey was carried out in eight communities of Sichuan between May 2015 and September 2015. The detailed procedures relating to recruitment of participants, evaluation of risk factors, and definition of high-risk stroke population were described in our previous articles (10,(14)(15)(16). Briefly, the eight communities were selected using the cluster randomization method.…”

“…The ultrasound investigators were blinded to the clinical data. The detailed procedure and definition for carotid plaques, mean IMT, degree of carotid stenosis, and intraobserver and interobserver coefficients can be found in our previous studies (10,(14)(15)(16). Carotid atherosclerosis was defined as mean IMT > 0.9 mm or the presence of any carotid plaque or any carotid stenosis ≥15% (16,18,19).…”

“…1 The detailed selection principle for the 19 SNPs has been described in our previous articles (10,16). In brief, (1) the SNPs were evaluated in our previous studies (10,(14)(15)(16); (2) the SNPs have a minor allele frequency > 0.05;…”

“…Atherosclerosis is a chronic inflammatory disease where the activation of various inflammatory cells, smooth muscle cell proliferation, and endothelial cell damage play key roles in the pathological mechanisms of atherosclerosis (11,12). Many studies have revealed that variants in genes related to inflammation and endothelial function are associated with carotid atherosclerosis (10,(13)(14)(15)(16). For instance, Gardener et al (13) evaluated the associations between carotid plaque and 197 variants in 43 genes implicated in inflammation and endothelial function and demonstrated that the variants in 10 genes (IL6R, TNF, NOS2A, IL1A, TNFSF4, ITGA2, PPARA, TLR4, HABP2, and VCAM1) were associated with carotid plaque in the Northern Manhattan population.…”