Objective:To make statistics on the distribution of ApoE gene polymorphism in the Longyan area,provide data for the statistics of regional cerebrovascular diseases,explore the significance of ApoE gene polymorphism di...Objective:To make statistics on the distribution of ApoE gene polymorphism in the Longyan area,provide data for the statistics of regional cerebrovascular diseases,explore the significance of ApoE gene polymorphism distribution for clinical guidance,diagnosis and treatment,and provide more suggestions for clinical diagnosis and treatment of cerebrovascular diseases.Methods:800 patients with cerebrovascular disease in the Longyan area from July 2018 to April 2021 were selected as the research object,and 800 normal healthy patients were selected as the control group.The data were further analyzed according to the collected patient information,and the patients were distinguished according to age and other basic information,the type of cerebrovascular disease,ApoE gene polymorphism and blood lipid test results.The distribution of ApoE gene polymorphism in the cerebrovascular disease population in the Longyan area was given to determine the correlation between the incidence of cerebrovascular disease and the distribution of ApoE gene polymorphism.Results:In the study group,E2/E3 genotyping was the most common 400(50.00%),and E4/E4 genotyping 6(0.75%)was the least common;In the control group,E2/E4 genotyping was the most common 480(60.00%),and E2/E3 genotyping accounted for the second 290(36.25%).In the study group,E3 allele was the most common 383(47.88%),E4 allele 121(15.12%);in the control group,E2 allele was the most common391(48.88%),and E3 allele 142(17.75%).Conclusion:According to the statistics of ApoE gene polymorphism distribution in the Longyan area and the analysis of the correlation of other cerebrovascular diseases,it is found that E2/E3 genotype may be related to cerebrovascular diseases,and E3 allele may be a susceptibility factor.Through the above analysis,the occurrence of diseases can be predicted and prevented.展开更多
Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the invol...Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the involvement of the APOE gene in the onset of T2DM and its vascular complications. Clinical and biochemical parameters were assessed in each participant. APOE genotypes were identified by PCR-RFLP. Arterial stiffness was studied using a pOpmetre<sup>®</sup> which evaluates the pulse wave velocity (ft-PWV). Endothelial dysfunction was studied using an EndoPAT2000<sup>®</sup> which measures endothelium-dependent vasodilation (RHI). In control subjects, the ε3 allele was associated with an increase in fasting blood glucose (r = 2.36, p = 0.018), and a decrease in LDL cholesterol levels (r = −2.17, p = 0.03), and ε4 was associated with an increase in total cholesterol (r = 2.59, p = 0.01), LDL cholesterol (r = 2.84, p = 0.004), and No-HDL cholesterol (r = 2.74, p = 0.006). In type 2 diabetes subjects, the ε2 was associated with a decrease in diastolic blood pressure (r = −2.25, p = 0.02). The ε3 was associated with a decrease in ft-PWV (r = −2.26, p = 0.024) while the ε4 was associated with an increase in ft-PWV (r = 2.52, p = 0.012). Carrying the ε2ε3 genotype would have in 99% a limited risk of developing T2DM, and in event of T2DM, only 1 to 2% would have a significant risk of developing atherosclerosis, which would be severe in 17%. Of the ε2ε4 genotype, 93% had a limited or even possible risk of developing T2DM, the remaining 7% had a very high risk of developing T2DM. Diabetics carrying ε2ε4 had in 7% very high risk of developing atherosclerosis. The latter had a 20% very high risk of being very severe. Subjects carrying the ε3ε4 genotype had a 67% possible or even probable risk of developing T2DM and in the event of diabetes, there was in 34% very high risk of developing atherosclerosis which will not have even the time to evolve towards severity. For subjects carrying the ε3ε3, the risk of developing T2DM and athérosclerosis was higher than that of the ε2ε3, and ε2ε4 genotypes but lower than that ε3ε4 genotype. The physio-pathological role of the APOE gene and the impacts of its polymorphisms are important in the onset and progression of type 2 diabetes mellitus.展开更多
The unusual chromosome 11q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases.However,its gene...The unusual chromosome 11q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases.However,its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed.We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing,association analyses,genetic fine mapping,and functional interpretation.The present study identified new meaningful genetic associations that were not simply determined by statistical significance.In addition to the APOA5 gene,we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids.Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses.rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility.Similarly,multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol.Our findings provided novel insights into this genomic locus in the Chinese population.展开更多
基金Longyan Science and Technology Planning Project,grant number:2018LYF5013
文摘Objective:To make statistics on the distribution of ApoE gene polymorphism in the Longyan area,provide data for the statistics of regional cerebrovascular diseases,explore the significance of ApoE gene polymorphism distribution for clinical guidance,diagnosis and treatment,and provide more suggestions for clinical diagnosis and treatment of cerebrovascular diseases.Methods:800 patients with cerebrovascular disease in the Longyan area from July 2018 to April 2021 were selected as the research object,and 800 normal healthy patients were selected as the control group.The data were further analyzed according to the collected patient information,and the patients were distinguished according to age and other basic information,the type of cerebrovascular disease,ApoE gene polymorphism and blood lipid test results.The distribution of ApoE gene polymorphism in the cerebrovascular disease population in the Longyan area was given to determine the correlation between the incidence of cerebrovascular disease and the distribution of ApoE gene polymorphism.Results:In the study group,E2/E3 genotyping was the most common 400(50.00%),and E4/E4 genotyping 6(0.75%)was the least common;In the control group,E2/E4 genotyping was the most common 480(60.00%),and E2/E3 genotyping accounted for the second 290(36.25%).In the study group,E3 allele was the most common 383(47.88%),E4 allele 121(15.12%);in the control group,E2 allele was the most common391(48.88%),and E3 allele 142(17.75%).Conclusion:According to the statistics of ApoE gene polymorphism distribution in the Longyan area and the analysis of the correlation of other cerebrovascular diseases,it is found that E2/E3 genotype may be related to cerebrovascular diseases,and E3 allele may be a susceptibility factor.Through the above analysis,the occurrence of diseases can be predicted and prevented.
文摘Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the involvement of the APOE gene in the onset of T2DM and its vascular complications. Clinical and biochemical parameters were assessed in each participant. APOE genotypes were identified by PCR-RFLP. Arterial stiffness was studied using a pOpmetre<sup>®</sup> which evaluates the pulse wave velocity (ft-PWV). Endothelial dysfunction was studied using an EndoPAT2000<sup>®</sup> which measures endothelium-dependent vasodilation (RHI). In control subjects, the ε3 allele was associated with an increase in fasting blood glucose (r = 2.36, p = 0.018), and a decrease in LDL cholesterol levels (r = −2.17, p = 0.03), and ε4 was associated with an increase in total cholesterol (r = 2.59, p = 0.01), LDL cholesterol (r = 2.84, p = 0.004), and No-HDL cholesterol (r = 2.74, p = 0.006). In type 2 diabetes subjects, the ε2 was associated with a decrease in diastolic blood pressure (r = −2.25, p = 0.02). The ε3 was associated with a decrease in ft-PWV (r = −2.26, p = 0.024) while the ε4 was associated with an increase in ft-PWV (r = 2.52, p = 0.012). Carrying the ε2ε3 genotype would have in 99% a limited risk of developing T2DM, and in event of T2DM, only 1 to 2% would have a significant risk of developing atherosclerosis, which would be severe in 17%. Of the ε2ε4 genotype, 93% had a limited or even possible risk of developing T2DM, the remaining 7% had a very high risk of developing T2DM. Diabetics carrying ε2ε4 had in 7% very high risk of developing atherosclerosis. The latter had a 20% very high risk of being very severe. Subjects carrying the ε3ε4 genotype had a 67% possible or even probable risk of developing T2DM and in the event of diabetes, there was in 34% very high risk of developing atherosclerosis which will not have even the time to evolve towards severity. For subjects carrying the ε3ε3, the risk of developing T2DM and athérosclerosis was higher than that of the ε2ε3, and ε2ε4 genotypes but lower than that ε3ε4 genotype. The physio-pathological role of the APOE gene and the impacts of its polymorphisms are important in the onset and progression of type 2 diabetes mellitus.
基金We gratefully acknowledge all the contributors that made this research possible,all the sample donors for this study,and all the clinicians for their assistance in recruiting participants to the study.This work was supported by the grant from the National Natural Science Foundation of China(31401082).
文摘The unusual chromosome 11q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases.However,its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed.We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing,association analyses,genetic fine mapping,and functional interpretation.The present study identified new meaningful genetic associations that were not simply determined by statistical significance.In addition to the APOA5 gene,we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids.Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses.rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility.Similarly,multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol.Our findings provided novel insights into this genomic locus in the Chinese population.
