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Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population

BACKGROUND AND METHODS: It has been reported that C/T dimorphism at position 1418 of the thrombomodulin gene causes a cytosine (C) transition to thymidine (T), resulting in an alanine (A) to valine (V) substitution at amino acid position 455 (TM455). TM455 had been found not only in African American...

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Autores principales: Qian, Gaochao, Ding, Zhixiang, Zhang, Binxia, Li, Qihua, Jin, Wentao, Zhang, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508656/
https://www.ncbi.nlm.nih.gov/pubmed/23204851
http://dx.doi.org/10.2147/JIR.S36510
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author Qian, Gaochao
Ding, Zhixiang
Zhang, Binxia
Li, Qihua
Jin, Wentao
Zhang, Qi
author_facet Qian, Gaochao
Ding, Zhixiang
Zhang, Binxia
Li, Qihua
Jin, Wentao
Zhang, Qi
author_sort Qian, Gaochao
collection PubMed
description BACKGROUND AND METHODS: It has been reported that C/T dimorphism at position 1418 of the thrombomodulin gene causes a cytosine (C) transition to thymidine (T), resulting in an alanine (A) to valine (V) substitution at amino acid position 455 (TM455). TM455 had been found not only in African American and American whites, but also in whites in The Netherlands and Sweden. Among these populations, the C/C genotype is predominant, although the distribution of this dimorphism is different. Thrombomodulin is an important anticoagulant protein that is downregulated in endothelial cells overlying atherosclerotic plaques and is also an anti-inflammatory molecule. TM455 is located in the last epidermal growth factor-like repeat of thrombomodulin, which is functionally important for protein C activation and thrombin binding. The distribution of thrombomodulin polymorphism and association between TM455, inflammatory cytokines, and carotid atherosclerosis in the Chinese Han population is unclear. METHODS: This thrombomodulin dimorphism was analyzed by allele-specific amplification in 144 patients with carotid atherosclerosis and in 384 healthy controls. TM455 was found in the Chinese Han population, but the genotype frequency and distribution of each genotype in this population differed substantially from that in other ethnic subgroups. The C/T and T/T genotypes were predominant in the Chinese Han population, and the frequency of the T allele in this population (63.8%) was much higher than that in whites in The Netherlands (18%), Sweden (26.1%), and the US (18.4%), and in blacks in the US (7.6%). The frequencies of these single nucleotide polymorphisms complied well with the Hardy-Weinberg equilibrium in healthy individuals. The C allele was significantly more common among patients with carotid atherosclerosis than in controls (P < 0.05). The frequency of the C allele was 45.5% in patients and 36.2% in controls. The thrombomodulin Ala455 genotypes C/C and C/T were significantly more common than the T/T genotype in patients with carotid atherosclerosis in the Chinese Han population. In addition, higher baseline levels of tumor necrosis factor alpha (55.45 ± 11.58 pg/mL versus 52.70 ± 10.74 pg/mL; P < 0.05), interleukin-6 (31.53 ± 10.51 pg/mL versus 27.73 ± 8.37 pg/mL; P < 0.01), and C-reactive protein (6.65 ± 2.01 mg/L versus 4.06 ± 1.03 mg/L; P < 0.01) were observed in patients with carotid atherosclerosis than in controls. Interestingly, compared with baseline inflammatory cytokine levels in those with the Val/Val genotype, higher baseline tumor necrosis factor alpha, interleukin-6, and C-reactive protein levels were observed for the Ala/Ala genotype in both patients with carotid atherosclerosis and healthy controls. CONCLUSION: Our results support a significant association between thrombomodulin Ala455Val dimorphism, inflammatory cytokines, and carotid atherosclerosis in the Chinese Han population.
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spelling pubmed-35086562012-11-30 Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population Qian, Gaochao Ding, Zhixiang Zhang, Binxia Li, Qihua Jin, Wentao Zhang, Qi J Inflamm Res Original Research BACKGROUND AND METHODS: It has been reported that C/T dimorphism at position 1418 of the thrombomodulin gene causes a cytosine (C) transition to thymidine (T), resulting in an alanine (A) to valine (V) substitution at amino acid position 455 (TM455). TM455 had been found not only in African American and American whites, but also in whites in The Netherlands and Sweden. Among these populations, the C/C genotype is predominant, although the distribution of this dimorphism is different. Thrombomodulin is an important anticoagulant protein that is downregulated in endothelial cells overlying atherosclerotic plaques and is also an anti-inflammatory molecule. TM455 is located in the last epidermal growth factor-like repeat of thrombomodulin, which is functionally important for protein C activation and thrombin binding. The distribution of thrombomodulin polymorphism and association between TM455, inflammatory cytokines, and carotid atherosclerosis in the Chinese Han population is unclear. METHODS: This thrombomodulin dimorphism was analyzed by allele-specific amplification in 144 patients with carotid atherosclerosis and in 384 healthy controls. TM455 was found in the Chinese Han population, but the genotype frequency and distribution of each genotype in this population differed substantially from that in other ethnic subgroups. The C/T and T/T genotypes were predominant in the Chinese Han population, and the frequency of the T allele in this population (63.8%) was much higher than that in whites in The Netherlands (18%), Sweden (26.1%), and the US (18.4%), and in blacks in the US (7.6%). The frequencies of these single nucleotide polymorphisms complied well with the Hardy-Weinberg equilibrium in healthy individuals. The C allele was significantly more common among patients with carotid atherosclerosis than in controls (P < 0.05). The frequency of the C allele was 45.5% in patients and 36.2% in controls. The thrombomodulin Ala455 genotypes C/C and C/T were significantly more common than the T/T genotype in patients with carotid atherosclerosis in the Chinese Han population. In addition, higher baseline levels of tumor necrosis factor alpha (55.45 ± 11.58 pg/mL versus 52.70 ± 10.74 pg/mL; P < 0.05), interleukin-6 (31.53 ± 10.51 pg/mL versus 27.73 ± 8.37 pg/mL; P < 0.01), and C-reactive protein (6.65 ± 2.01 mg/L versus 4.06 ± 1.03 mg/L; P < 0.01) were observed in patients with carotid atherosclerosis than in controls. Interestingly, compared with baseline inflammatory cytokine levels in those with the Val/Val genotype, higher baseline tumor necrosis factor alpha, interleukin-6, and C-reactive protein levels were observed for the Ala/Ala genotype in both patients with carotid atherosclerosis and healthy controls. CONCLUSION: Our results support a significant association between thrombomodulin Ala455Val dimorphism, inflammatory cytokines, and carotid atherosclerosis in the Chinese Han population. Dove Medical Press 2012-11-15 /pmc/articles/PMC3508656/ /pubmed/23204851 http://dx.doi.org/10.2147/JIR.S36510 Text en © 2012 Qian et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Qian, Gaochao
Ding, Zhixiang
Zhang, Binxia
Li, Qihua
Jin, Wentao
Zhang, Qi
Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
title Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
title_full Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
title_fullStr Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
title_full_unstemmed Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
title_short Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
title_sort association of thrombomodulin ala455val dimorphism and inflammatory cytokines with carotid atherosclerosis in the chinese han population
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508656/
https://www.ncbi.nlm.nih.gov/pubmed/23204851
http://dx.doi.org/10.2147/JIR.S36510
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