Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke

Hsin Bang Leu, Chia Min Chung, Shao Yuan Chuang, Chyi-Huey Bai, Jiunn Rong Chen, Jaw Wen Chen, W. H. Pan

研究成果: 雜誌貢獻文章

32 引文 (Scopus)

摘要

Background: Carotid intima-medial thickness (IMT) is a surrogate marker of subclinical atherosclerosis. This study aimed to investigate the impacts of genetic variants on IMT and future development of ischemic stroke in a cohort, followed by an independent replication study. Methods: B-mode carotid ultrasound was performed among 3330 healthy adults in the CVDFACT cohort study, and the genetic effects of atherosclerosis-related genes including connexin37 (GJA4), C-reactive protein (CRP), paraoxonase (PON1), adiponectin (ACDC), angiotensin-converting enzyme (ACE), beta-adrenergic receptor (ADRB1, ADRB2), antithrombin III (SERPINC1), and kinesin family member 6 (KIF6) were evaluated by a multivariate regression model, adjusting for traditional vascular risk factors. Study subjects were prospectively followed for the development of ischemic stroke to assess the prognostic impacts of these genetic variants. An independent case-control study was performed to replicate the genetic association from the cohort study. Results: The T allele of connexin37 C1019T polymorphism significantly affected IMT (β= 0.014, p= 0.013) after adjusting for traditional risk factors. During an average follow-up period of 10.7 years, 80 patients with ischemic stroke (2.4%) were identified. The connexin37 1019. T allele was significantly associated with an increased rate of ischemic stroke under an additive model, with hazard ratios (HR) of 2.83 (95% confidence interval, 1.2-6.66) and 1.69 (95% confidence interval, 1.06-2.71), comparing TT and CT genotype with CC, respectively. After Cox analysis, age (HR, 1.78 every 10 years), diabetes mellitus (HR, 2.63), hypertension (HR, 2.08), and the T allele of C1019T polymorphism of GJA4 (HR, 1.69) were identified as independent predictors of ischemic stroke. The relationship between T allele of C1019T polymorphism of GJA4 gene and ischemic stroke was also confirmed by an independent association study. Conclusion: Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke.
原文英語
頁(從 - 到)101-106
頁數6
期刊Atherosclerosis
214
發行號1
DOIs
出版狀態已發佈 - 一月 2011

指紋

Stroke
Alleles
Atherosclerosis
Cohort Studies
Confidence Intervals
Aryldialkylphosphatase
Kinesin
Antithrombin III
Receptors, Adrenergic, beta
Adiponectin
Genetic Association Studies
Peptidyl-Dipeptidase A
Proportional Hazards Models
C-Reactive Protein
Genes
Case-Control Studies
Diabetes Mellitus
Biomarkers
Genotype
Hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

引用此文

Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke. / Leu, Hsin Bang; Chung, Chia Min; Chuang, Shao Yuan; Bai, Chyi-Huey; Chen, Jiunn Rong; Chen, Jaw Wen; Pan, W. H.

於: Atherosclerosis, 卷 214, 編號 1, 01.2011, p. 101-106.

研究成果: 雜誌貢獻文章

Leu, Hsin Bang ; Chung, Chia Min ; Chuang, Shao Yuan ; Bai, Chyi-Huey ; Chen, Jiunn Rong ; Chen, Jaw Wen ; Pan, W. H. / Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke. 於: Atherosclerosis. 2011 ; 卷 214, 編號 1. 頁 101-106.
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title = "Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke",
abstract = "Background: Carotid intima-medial thickness (IMT) is a surrogate marker of subclinical atherosclerosis. This study aimed to investigate the impacts of genetic variants on IMT and future development of ischemic stroke in a cohort, followed by an independent replication study. Methods: B-mode carotid ultrasound was performed among 3330 healthy adults in the CVDFACT cohort study, and the genetic effects of atherosclerosis-related genes including connexin37 (GJA4), C-reactive protein (CRP), paraoxonase (PON1), adiponectin (ACDC), angiotensin-converting enzyme (ACE), beta-adrenergic receptor (ADRB1, ADRB2), antithrombin III (SERPINC1), and kinesin family member 6 (KIF6) were evaluated by a multivariate regression model, adjusting for traditional vascular risk factors. Study subjects were prospectively followed for the development of ischemic stroke to assess the prognostic impacts of these genetic variants. An independent case-control study was performed to replicate the genetic association from the cohort study. Results: The T allele of connexin37 C1019T polymorphism significantly affected IMT (β= 0.014, p= 0.013) after adjusting for traditional risk factors. During an average follow-up period of 10.7 years, 80 patients with ischemic stroke (2.4{\%}) were identified. The connexin37 1019. T allele was significantly associated with an increased rate of ischemic stroke under an additive model, with hazard ratios (HR) of 2.83 (95{\%} confidence interval, 1.2-6.66) and 1.69 (95{\%} confidence interval, 1.06-2.71), comparing TT and CT genotype with CC, respectively. After Cox analysis, age (HR, 1.78 every 10 years), diabetes mellitus (HR, 2.63), hypertension (HR, 2.08), and the T allele of C1019T polymorphism of GJA4 (HR, 1.69) were identified as independent predictors of ischemic stroke. The relationship between T allele of C1019T polymorphism of GJA4 gene and ischemic stroke was also confirmed by an independent association study. Conclusion: Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke.",
keywords = "Connexin37, Intima-medial thickness, Ischemic stroke",
author = "Leu, {Hsin Bang} and Chung, {Chia Min} and Chuang, {Shao Yuan} and Chyi-Huey Bai and Chen, {Jiunn Rong} and Chen, {Jaw Wen} and Pan, {W. H.}",
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T1 - Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke

AU - Leu, Hsin Bang

AU - Chung, Chia Min

AU - Chuang, Shao Yuan

AU - Bai, Chyi-Huey

AU - Chen, Jiunn Rong

AU - Chen, Jaw Wen

AU - Pan, W. H.

PY - 2011/1

Y1 - 2011/1

N2 - Background: Carotid intima-medial thickness (IMT) is a surrogate marker of subclinical atherosclerosis. This study aimed to investigate the impacts of genetic variants on IMT and future development of ischemic stroke in a cohort, followed by an independent replication study. Methods: B-mode carotid ultrasound was performed among 3330 healthy adults in the CVDFACT cohort study, and the genetic effects of atherosclerosis-related genes including connexin37 (GJA4), C-reactive protein (CRP), paraoxonase (PON1), adiponectin (ACDC), angiotensin-converting enzyme (ACE), beta-adrenergic receptor (ADRB1, ADRB2), antithrombin III (SERPINC1), and kinesin family member 6 (KIF6) were evaluated by a multivariate regression model, adjusting for traditional vascular risk factors. Study subjects were prospectively followed for the development of ischemic stroke to assess the prognostic impacts of these genetic variants. An independent case-control study was performed to replicate the genetic association from the cohort study. Results: The T allele of connexin37 C1019T polymorphism significantly affected IMT (β= 0.014, p= 0.013) after adjusting for traditional risk factors. During an average follow-up period of 10.7 years, 80 patients with ischemic stroke (2.4%) were identified. The connexin37 1019. T allele was significantly associated with an increased rate of ischemic stroke under an additive model, with hazard ratios (HR) of 2.83 (95% confidence interval, 1.2-6.66) and 1.69 (95% confidence interval, 1.06-2.71), comparing TT and CT genotype with CC, respectively. After Cox analysis, age (HR, 1.78 every 10 years), diabetes mellitus (HR, 2.63), hypertension (HR, 2.08), and the T allele of C1019T polymorphism of GJA4 (HR, 1.69) were identified as independent predictors of ischemic stroke. The relationship between T allele of C1019T polymorphism of GJA4 gene and ischemic stroke was also confirmed by an independent association study. Conclusion: Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke.

AB - Background: Carotid intima-medial thickness (IMT) is a surrogate marker of subclinical atherosclerosis. This study aimed to investigate the impacts of genetic variants on IMT and future development of ischemic stroke in a cohort, followed by an independent replication study. Methods: B-mode carotid ultrasound was performed among 3330 healthy adults in the CVDFACT cohort study, and the genetic effects of atherosclerosis-related genes including connexin37 (GJA4), C-reactive protein (CRP), paraoxonase (PON1), adiponectin (ACDC), angiotensin-converting enzyme (ACE), beta-adrenergic receptor (ADRB1, ADRB2), antithrombin III (SERPINC1), and kinesin family member 6 (KIF6) were evaluated by a multivariate regression model, adjusting for traditional vascular risk factors. Study subjects were prospectively followed for the development of ischemic stroke to assess the prognostic impacts of these genetic variants. An independent case-control study was performed to replicate the genetic association from the cohort study. Results: The T allele of connexin37 C1019T polymorphism significantly affected IMT (β= 0.014, p= 0.013) after adjusting for traditional risk factors. During an average follow-up period of 10.7 years, 80 patients with ischemic stroke (2.4%) were identified. The connexin37 1019. T allele was significantly associated with an increased rate of ischemic stroke under an additive model, with hazard ratios (HR) of 2.83 (95% confidence interval, 1.2-6.66) and 1.69 (95% confidence interval, 1.06-2.71), comparing TT and CT genotype with CC, respectively. After Cox analysis, age (HR, 1.78 every 10 years), diabetes mellitus (HR, 2.63), hypertension (HR, 2.08), and the T allele of C1019T polymorphism of GJA4 (HR, 1.69) were identified as independent predictors of ischemic stroke. The relationship between T allele of C1019T polymorphism of GJA4 gene and ischemic stroke was also confirmed by an independent association study. Conclusion: Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke.

KW - Connexin37

KW - Intima-medial thickness

KW - Ischemic stroke

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