Dataset Information

Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China.

ABSTRACT:

Aim

To evaluate the relationship between carotid stenosis with variants in genes referred to inflammation and endothelial function.

Methods

There was a multi-center, cross sectional survey in southwestern China. The eight communities were selected at random in southwestern China. The residents aged ≥40 years volunteered to participate in face-to-face survey. Subjects with at least three of the aforementioned eight stroke related risk factors or a history of stroke were classified as high-risk population for stroke. A total of 2,377 subjects were the high-risk population for stroke in the eight communities, and degree of carotid stenosis was assessed by carotid ultrasound. Genotypes of 6 variants in 3 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR).

Results

Carotid stenosis were found in 295 (12.41%) subjects, of whom 51 (17.29%) had moderate or severe stenosis. According to multivariate logistic regression analysis, we found that HABP2rs7923349TT was independent risk factor for carotid stenosis (OR, 1.96, 95% CI: 1.22-3.13, P = 0.005) and ITGA2rs1991013AG and HABP2rs7923349TT were independent risk factors for moderate to severe carotid stenosis (OR, 2.28, 95% CI: 1.28-4.07, P = 0.005; OR, 2.90, 95% CI: 1.19-7.08, P = 0.019). GMDR analysis showed that there was a significant gene-gene interaction between ITGA2 rs4865756 and HABP2 rs7923349, and the high-risk interactive genotype in the two variants was independently associated with a higher risk for carotid stenosis after adjusting the covariates (OR,1. 42, 95% CI 1.10-1.84, P = 0.008).

Conclusions

Prevalence of carotid stenosis was very high in the high-risk stroke population in southwestern China. Variants in genes referred in endothelial function were associated with the carotid stenosis. The high-risk interactive genotype in ITGA2 rs4865756 and HABP2 rs7923349 was independently associated with a higher risk for carotid stenosis.

SUBMITTER: Liu L

PROVIDER: S-EPMC9848733 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China.

Liu Lin L Yi Xingyang X Luo Hua H Yu Ming M

Frontiers in neurology 20230104

<h4>Aim</h4>To evaluate the relationship between carotid stenosis with variants in genes referred to inflammation and endothelial function.<h4>Methods</h4>There was a multi-center, cross sectional survey in southwestern China. The eight communities were selected at random in southwestern China. The residents aged ≥40 years volunteered to participate in face-to-face survey. Subjects with at least three of the aforementioned eight stroke related risk factors or a history of stroke were classified ...[more]

PMID: 36686520

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Project description:AimTo investigate the potential association between polymorphisms in genes involved in endothelial function, inflammation and carotid atherosclerosis.MethodsThis was a three-center, population-based sectional survey conducted in Sichuan province of southwestern China. We randomly selected 8 different communities in Sichuan, and the residents in each community volunteered to participate in the survey by face-to-face questionnaire. A total of 2,377 residents with high stroke risk population in the 8 communities were included. Carotid atherosclerosis was evaluated by carotid ultrasound, and the 19 single nucleotide polymorphisms (SNPs) in 10 endothelial function as well as inflammation relevant genes were measured in the high stroke risk population. Carotid atherosclerosis was defined by the presence of carotid plaque or any carotid stenosis ≥15% or mean intima-media thickness (IMT) > 0.9 mm. Generalized multifactor dimensionality reduction (GMDR) approach was used to analyze gene-gene interactions among the 19 SNPs.ResultsAmong the 2,377 subjects with high stroke risk, 1,028 subjects had carotid atherosclerosis (43.2%), of which 852 (35.8%) cases had carotid plaque, 295 (12.4%) cases had ≥15% carotid stenosis, whereas 445 (18.7%) had mean IMT > 0.9 mm. Multivariate logistic regression revealed that IL1A rs1609682 TT and HABP2 rs7923349 TT served as independent risk factors for carotid atherosclerosis (OR, 1.45, 95% CI: 1.034-2.032, p = 0.031, and OR, 1.829, 95% CI: 1.228-2.723, p = 0.003). GMDR analysis indicated that there was a significant gene-gene interaction found among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349. After adjusting the covariates, the high-risk interactive genotypes in the 3 variants were significantly associated with a significantly higher risk for carotid atherosclerosis (OR, 2.08, 95% CI: 1.257-5.98, p < 0.001).ConclusionThe prevalence of carotid atherosclerosis was observed to be extremely high in the high-risk stroke population in southwestern China. There were associations observed between the specific variants in inflammation and endothelial function relevant genes and carotid atherosclerosis. The high-risk interactive genotypes among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349 significantly increased the risk of carotid atherosclerosis. These results are expected to provide novel strategies for the prevention of carotid atherosclerosis. The gene-gene interactive analysis used in this study may be very helpful to elucidate complex genetic risk factors for carotid atherosclerosis.

Project description:Objectives: We aimed to explore sex-specific association between genes involved in inflammation and endothelial function and vulnerable carotid plaque, a subclinical precursor of ischemic stroke. Methods: Carotid plaque and plaque phenotype were assessed by carotid ultrasound in high-risk participants for stroke drawn from a multicenter, cross-sectional survey in southwestern China. We examined 18 single nucleotide polymorphisms (SNPs) in 10 genes related to inflammation and endothelial function. Sex differences in the genotype of the candidate SNPs and risk of vulnerable carotid plaques were assessed. Interaction tests were performed to identify the SNPs that might modify the association between the sex and vulnerable plaques. For SNPs with suggestive evidence for interaction with sex (p for interaction<0.05), stratification analysis by sex was performed to evaluate the sex-specific association between the SNP and vulnerable plaques. Results: 2,644 high-risk individuals were enrolled, comprising 1,202 (45.5%) men and 1,442 (54.5%) women. Vulnerable carotid plaques were detected in 425 (16.1%) participants. Among candidate SNPs, the genotype frequencies of 5 SNPs (TNFSF4 rs11811788, TNFSF4 rs1234313, IL6R rs4845625, VCAM1 rs2392221, and ITGA2 rs1991013) were significantly different between sex (all p < 0.05). Univariable and multivariable analyses suggested that male individuals had a significantly higher prevalence of vulnerable carotid plaques (20.0% vs. 12.8%, adjusted OR 1.72, 95% CI 1.12-2.66, p = 0.014), while none of the candidate SNPs was significantly associated with vulnerable plaques (all p > 0.05). Interaction tests found the association between sex and vulnerable plaques is affected by the genotype of IL6R rs4845625 (p for interaction = 0.031). Stratification analysis revealed a strong association between IL6R rs4845625 and vulnerable carotid plaque in man (dominant model TT vs. CT + CC: adjusted OR 1.52, 95% CI 1.12-2.07, p = 0.007; codominant model TT vs. CC: adjusted OR 1.50, 95% CI 1.00-2.25, p = 0.048) but not in women (p > 0.05 in all genetic models). Conclusion: The rs4845625 polymorphism in IL6R has sex-specific effects on vulnerable carotid plaque in Chinese Han high-risk individuals for stroke. Our findings provide a plausible genetic basis underlying the sex difference in carotid plaque vulnerability.

Project description:ObjectivePrior studies have shown that plaque inflammation on FDG-PET and the symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score were associated with recurrent ischemic events, but the findings have thus far not been widely validated. Therefore, we aimed to validate the findings of prior studies.MethodsA single-center prospective cohort study that recruited patients with (1) recent TIA or ischemic stroke within the past 30 days, (2) ipsilateral carotid artery stenosis of ≥50%, and (3) were not considered for early carotid revascularization. The (1) maximum standardized uptake value (SUVmax) of the symptomatic carotid plaque, (2) the SCAIL score, and (3) stenosis severity of the symptomatic carotid artery were measured for all patients. The outcomes were (1) a 90-day ipsilateral ischemic stroke and (2) a 90-day ipsilateral symptomatic TIA or major adverse cardiovascular event (MACE).ResultsAmong the 131 patients included in the study, the commonest cardiovascular risk factor was hypertension (95 patients, 72.5%), followed by diabetes mellitus (77 patients, 58.8%) and being a current smoker (64 patients, 48.9%). The median (IQR) duration between the index cerebral ischemic event and recruitment to the study was 1 (0, 2.5) days. The median (IQR) duration between the index cerebral ischemic event and FDG-PET was 5 (4, 7) days. A total of 14 (10.7%) patients had a 90-day stroke, and 41 (31.3%) patients had a 90-day TIA or MACE. On comparison of the predictive performances of the SCAIL score and SUVmax, SUVmax was found to be superior to the SCAIL score for predicting both 90-day ipsilateral ischemic stroke (AUC: SCAIL = 0.79, SUVmax = 0.92; p < 0.001; 95% CI = 0.072, 0.229) and 90-day TIA or MACE (AUC: SCAIL = 0.76, SUVmax = 0.84; p = 0.009; 95% CI = 0.020, 0.143).ConclusionPlaque inflammation as quantified on FDG-PET may serve as a reliable biomarker for risk stratification among patients with ECAD and recent TIA or ischemic stroke. Future studies should evaluate whether patients with significant plaque inflammation as quantified on FDG-PET benefit from carotid revascularization and/or anti-inflammatory therapy.

Project description:In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50-69% stenosis, 70-90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class - including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.

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Dataset Information

Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China.

Aim

Methods

Results

Conclusions

Publications

Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China.

Similar Datasets

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