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

Gaochao Qian,1 Zhixiang Ding,1 Binxia Zhang,2 Qihua Li,2 Wentao Jin,1 Qi Zhang21Clinical Laboratory Department, 2Department of Cardiology, Changzhou TCM Hospital Affiliated to Nanjing TCM University, Changzhou, ChinaBackground and methods: It has been reported that C/T dimorphism at position 1418 of...

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Autores principales:	Qian G, Ding Z, Zhang B, Li Q, Jin W, Zhang Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b6d99b254cb24506ba613a90cf26bce0
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spelling	oai:doaj.org-article:b6d99b254cb24506ba613a90cf26bce02021-12-02T08:47:52ZAssociation of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population1178-7031https://doaj.org/article/b6d99b254cb24506ba613a90cf26bce02012-11-01T00:00:00Zhttp://www.dovepress.com/association-of-thrombomodulin-ala455val-dimorphism-and-inflammatory-cy-a11528https://doaj.org/toc/1178-7031Gaochao Qian,1 Zhixiang Ding,1 Binxia Zhang,2 Qihua Li,2 Wentao Jin,1 Qi Zhang21Clinical Laboratory Department, 2Department of Cardiology, Changzhou TCM Hospital Affiliated to Nanjing TCM University, Changzhou, ChinaBackground 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 &lt; 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 &plusmn; 11.58 pg/mL versus 52.70 &plusmn; 10.74 pg/mL; P &lt; 0.05), interleukin-6 (31.53 &plusmn; 10.51 pg/mL versus 27.73 &plusmn; 8.37 pg/mL; P &lt; 0.01), and C-reactive protein (6.65 &plusmn; 2.01 mg/L versus 4.06 &plusmn; 1.03 mg/L; P &lt; 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.Keywords: thrombomodulin, carotid atherosclerosis, dimorphism, inflammatory cytokines, association studyQian GDing ZZhang BLi QJin WZhang QDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2012, Iss default, Pp 117-123 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Qian G Ding Z Zhang B Li Q Jin W Zhang Q Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population
description	Gaochao Qian,1 Zhixiang Ding,1 Binxia Zhang,2 Qihua Li,2 Wentao Jin,1 Qi Zhang21Clinical Laboratory Department, 2Department of Cardiology, Changzhou TCM Hospital Affiliated to Nanjing TCM University, Changzhou, ChinaBackground 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 &lt; 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 &plusmn; 11.58 pg/mL versus 52.70 &plusmn; 10.74 pg/mL; P &lt; 0.05), interleukin-6 (31.53 &plusmn; 10.51 pg/mL versus 27.73 &plusmn; 8.37 pg/mL; P &lt; 0.01), and C-reactive protein (6.65 &plusmn; 2.01 mg/L versus 4.06 &plusmn; 1.03 mg/L; P &lt; 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.Keywords: thrombomodulin, carotid atherosclerosis, dimorphism, inflammatory cytokines, association study
format	article
author	Qian G Ding Z Zhang B Li Q Jin W Zhang Q
author_facet	Qian G Ding Z Zhang B Li Q Jin W Zhang Q
author_sort	Qian G
title	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_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_sort	association of thrombomodulin ala455val dimorphism and inflammatory cytokines with carotid atherosclerosis in the chinese han population
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/b6d99b254cb24506ba613a90cf26bce0
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Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population

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