Polymorphism in Integrin ITGA2 is Associated with Ischemic Stroke and Altered Serum Cholesterol in Chinese Individuals

Lü, Jian; Lu, Zhong; Zhang, Shao lan; Zhi, Juan; Chen, Zheng Ping; Wang, Wan Xiang

doi:10.5152/balkanmedj.2013.7993

Cited by 20 publications

(14 citation statements)

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“…Finally, 28 studies in Chinese and 32 in English were eligible for the meta-analysis on the different genetic variants of the GP genes. Of them, 56 studies were full-length reports published in peer-reviewed journals 31–86 and 4 were thesis of Master’s degree. 87–90 The characteristics of studies included and polymorphisms involved in this review are summarized in Tables 1 and 2, while a summary of the total number of studies on different genetic variants of the GP genes, including the number of cases and controls and proportion of those studies originating from Caucasian or Asian populations are provided in Table 3.…”

Section: Resultsmentioning

confidence: 99%

Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis

Liu

Wang

Zheng

et al. 2016

International Journal of Stroke

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Background/aims Platelet glycoproteins play a crucial role in the initial stage of thrombus formation and may contribute to the pathophysiology of atherosclerosis. Polymorphisms in glycoprotein genes alter the function of the protein, possibly leading to increased risk of ischemic stroke. However, previous genetic association studies that examined the relationship between glycoprotein genes polymorphisms and ischemic stroke have yielded inconsistent results. This study aimed to evaluate the association between glycoprotein genes and ischemic stroke by the application of meta-analysis. Methods Relevant studies were identified by an extensive search through databases. The quality of included studies was assessed independently using the Newcastle-Ottawa Scale. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and a meta-regression model was used to explore the study-level variables and to describe the heterogeneity in included studies. Egger's test and funnel plot were used to assess publication bias. Results A total of 60 studies (9 polymorphisms) were included and identified in the current meta-analysis. The Newcastle-Ottawa Scale scores ranged from 7 to 9 except for two studies with Newcastle-Ottawa Scale scores of 6. The T allele or TT genotype of the glycoprotein Ia C807T polymorphism were associated with an increased susceptibility to ischemic stroke in combined population (807T allele: OR, 95%CI: 1.24, 1.03-1.50, p = 0.02) or Asian populations (807T allele: OR, 95%CI: 1.31, 1.10-1.54, p = 0.002 and 807TT genotype: OR, 95%CI: 1.53, 1.13-2.08, p = 0.006, respectively), and the Ser allele of HPA-3 was associated with increased risk of ischemic stroke in combined population or in Asians (OR, 95%CI: 1.21, 1.04-1.40, p = 0.01 or 1.54, 1.18-2.01, p = 0.001). Of note, the Ser/Ser genotype was more common in Asians (OR, 95%CI: 2.09, 1.40-3.13, p < 0.001). For glycoprotein Ibα variable number tandem repeat, only B allele showed a mild significant association with ischemic stroke risk in combined population or in Caucasians (OR, 95%CI: 2.17, 1.04-4.55, p = 0.04 or 1.79, 1.02-3.13, p = 0.04). There was no significant association between HPA-1, HPA-2, HPA-4, HPA-5, glycoprotein Ibα-5 T/C as well as Ia G873A polymorphisms and increased risk of ischemic stroke. Conclusions We found that glycoprotein Ia C807T T allele or the TT genotype, the Ser-allele of HPA-3 and B allele of glycoprotein Ibα variable number tandem repeat polymorphisms were associated with increased risk for ischemic stroke. Future studies with larger sample sizes will be necessary to confirm the results. In addition, analyses of ischemic stroke subtypes and gene-gene and gene-environment interactions are warranted.

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Section: Resultsmentioning

confidence: 99%

Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis

Liu

Wang

Zheng

et al. 2016

International Journal of Stroke

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“…The frequency of T allele in AR group was higher than that in AS group, the difference was statistically significant, suggesting that carrying 807T allele in women increased the incidence of biochemical AR. Studies have found that the expression of the 807T allele increased the level of cholesterol from atherosclerosis 18. In this study, genotype CT + TT/CC grouping, compared between the two groups of total cholesterol, low‐density lipoprotein, blood glucose, uric acid, and other related factors, no significant differences were found, and the mechanism need for further study.…”

Section: Discussionmentioning

confidence: 70%

Association of GPIa and COX‐2 gene polymorphism with aspirin resistance

Wang

Sun

Dong

et al. 2017

Clinical Laboratory Analysis

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ObjectiveThis study aimed to explore the association between GPIa, COX‐2 gene polymorphisms and aspirin resistance in the ischemic stroke patients from the southern part of Jiangsu province.MethodsIn all, 97 patients with acute ischemic stroke were enrolled in the study. GPIa gene polymorphism at 807C>T (rsl126643) locus and COX‐2 gene polymorphism at ‐765G>C (rs20417) locus were genotyped by PCR pyrosequencing technology. Patients were divided into the aspirin sensitivity (AS) group and aspirin resistance (AR) group according to the platelet aggregation rate. The relationship between the two gene polymorphisms and aspirin resistance was investigated and analyzed.ResultsThe distribution of the genotype (CC, CT, TT, CT + TT, and CC) and the frequency of allele T of GPIa gene at 807C>T locus were significantly different in AS and AR groups in female patients (P < .05). Logistic regression analysis showed that the genotype of CT+TT at 807C>T locus was significantly correlated with AR after adjustment for relative factors (P = .047, OR = 4.856, 95% CI: 1.020–23.108). There were no significant differences in the genotype distribution and allele frequency of the COX‐2 gene ‐765G>C site between two groups (P > .05).Conclusion GPIa gene polymorphism at 807C>T locus was associated with AR in Chinese Han females, and the expression of allele T increased the incidence of AR. The gene polymorphism of COX‐2 gene at ‐765G>C locus was not significantly correlated with AR.

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“…As a key member of the integrin family of adhesion molecules, ITGA2 mediates cell-cell, cell-matrix, and cell-matrix-cell adhesions [ 17 ]. It therefore affects various physiological and pathological processes such as inflammatory reactions, immune responses, atherosclerosis, and thrombosis [ 18 ]. KD is characterized by multisystem involvement and inflammation of all medium-sized arteries, including the coronary artery [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Integrin α2 gene polymorphism is a risk factor of coronary artery lesions in Chinese children with Kawasaki disease

Yuan

Jiang

et al. 2021

Pediatr Rheumatol

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Background Kawasaki disease (KD) is a systemic vasculitis, and the formation of coronary artery lesions(CAL) is its most common sequela. Both genetic and environmental factors are considered to be important factors of in KD. Integrin α2 (ITGA2) is a transmembrane receptor that is associated with susceptibility to several diseases, but its relevance to KD with CAL is unclear. Methods We genotyped ITGA2 rs1126643 in 785 KD patients with the CAL and no-CAL(NCAL) (300 patients with CAL, and 485 age- and sex-matched patients with NCAL). OR (95% CI) and adjusted OR (95% CI) were used to evaluate the intensity of the association. Results We found a significantly increased risk of KD with CAL associated with ITGA2 rs1126643 genotypes (CT vs CC: adjusted OR = 1.57, 95% CI = 1.16–2.12, P = 0.0032; CT/TT vs CC: adjusted OR = 1.49, 95% CI = 1.12–2.00, P = 0.0068; T vs C: adjusted OR = 1.66, 95% CI = 1.16–2.51, P = 0.0165). Moreover, we found that carriers of the CT/TT genotype had a significant risk of KD with coronary artery lesion susceptibility for children ≤60 months of age, and the CT/TT genotype was significantly associated with an increased risk of SCAL formation and MCAL formation when compared with the CC genotype. Conclusion ITGA2 rs1126643 was associated with increased susceptibility and severity of CAL in KD.

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Polymorphism in Integrin ITGA2 is Associated with Ischemic Stroke and Altered Serum Cholesterol in Chinese Individuals

Cited by 20 publications

References 6 publications

Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis

Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis

Association of GPIa and COX‐2 gene polymorphism with aspirin resistance

Integrin α2 gene polymorphism is a risk factor of coronary artery lesions in Chinese children with Kawasaki disease

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