Correlation Between RP11-386M24.6 Gene Polymorphism Of Ischemic Stroke,Coronary Heart Disease With Phlegm And Blood Stasis Syndrome From The Perspective Of “Different Disease With The Same Syndromes Of TCM”

Objective:In this study,we investigated the susceptibility of RP11-386M24.6 single nucleotide polymorphism to ischemic stroke and coronary heart disease with phlegm and blood stasis syndrome,as well as the relationship between RP11-386M24.6 single nucleotide polymorphism and clinical indicators in patients with ischemic stroke and coronary heart disease with phlegm and blood stasis syndrome,with the aim of discovering potential biological markers of"different diseases with the same syndrome"in traditional Chinese medicine.Methods:The investigation involved three groups,533 patients with phlegm-stasis syndrome of ischemic stroke,500 patients with phlegm-stasis syndrome of coronary heart disease and 531 controls were included.The RP11-386M24.6 polymorphisms（rs17647695,rs17704159,rs28692833）were genotyped by Mass ARRAY platform.Coagulation,blood lipid,blood glucose,uric acid,homocysteine and C-reactive protein levels in patients with phlegm-stasis syndrome of IS and CHD were detected by coagulation,resistance,enzyme kinetic colorimetry,enzyme-enzymatic method and immunoturbidimetry.Statistical and genetic association analyses were conducted using SPSS and PLINK software.Results:（1）In the additive,dominant and recessive model genetic models,no statistically significant differences were found in the association of RP11-386M24.6 single nucleotide rs17647695,rs28692833 and rs17704159polymorphisms with the risk of IS and CHD sputum stasis,(all P,P_adj>0.05).（2）In the additive model,dominant model and recessive model genetic model,RP11-386M24.6 single nucleotide rs17647695,rs28692833,rs17704159 polymorphisms were not found to be associated with blood pressure levels（systolic and diastolic blood pressure）in patients with IS and CHD phlegm and blood stasis syndrome,and the differences were not statistically significant(all P,P_adj>0.05).（3）In the additive model,dominant model and recessive model genetic models,no RP11-386M24.6 single nucleotide rs17647695,rs28692833,rs17704159 polymorphisms were found to be associated with blood glucose levels（fasting blood glucose,2h postprandial blood glucose）in patients with IS phlegm and blood stasis syndrome,and the differences were not statistically significant(all P,P_adj>0.05);RP11-386M24.6 single nucleotide rs28692833 polymorphism was associated with fasting blood glucose in patients with CHD phlegm and blood stasis syndrome(additive model:β^b（95%CI）=3.211（1.30-5.13）,P_adj=0.001;recessive model:β^b（95%CI）=10.740（6.06-15.42）,P_adj=0.000)were significantly correlated.（4）RP11-386M24.6 single nucleotide polymorphism rs28692833polymorphism was significantly associated with total cholesterol in patients with IS phlegm and blood stasis syndrome(additive model:β^b（95%CI）=1.320（0.14-2.50）,P_adj=0.029;recessive model:β^b（95%CI）=4.355（1.67-7.04）,P_adj=0.002),Apo-A1(recessive model:β^b（95%CI）=0.107（0.01-0.20）,P_adj=0.025)were significantly correlated;RP11-386M24.6 single nucleotide polymorphism rs28692833polymorphism was significantly associated with total cholesterol in patients with phlegm and blood stasis syndrome of CHD(additive model:β^b（95%CI）=0.666（0.06-1.27）,P_adj=0.031;recessive model:β^b（95%CI）=2.321（0.92-3.72）,P_adj=0.001)significantly correlated.（5）RP11-386M24.6 single nucleotide rs17647695 polymorphism was significantly associated with prothrombin activity in patients with IS phlegm and blood stasis syndrome(additive model:β^b（95%CI）=3.043（0.56-5.53）,P_adj=0.017;dominant model:β^b（95%CI）=3.643（0.42-6.87）,P_adj=0.027)significantly correlated;RP11-386M24.6 single nucleotide rs17647695 polymorphism was significantly associated with prothrombin time of patients with CHD phlegm and blood stasis syndrome(recessive model:β^b（95%CI）=4.318（0.70-7.94）,P_adj=0.019);RP11-386M24.6 single nucleotide rs28692833 polymorphism was significantly correlated with prothrombin time of patients with CHD phlegm and blood stasis syndrome(recessive model:β^b（95%CI）=4.318（0.70-7.94）,P_adj=0.019);additive model:β^b（95%CI）=0.923（0.22-1.63）,P_adj=0.010;recessive model:β^b（95%CI）=3.262（1.50-5.03）,P_adj=0.000),international normalized ratio(additive model:β^b（95%CI）=0.200（0.02-0.38）,P_adj=0.026;recessive model:β^b（95%CI）=0.574（0.13-1.01）,P_adj=0.011),and fibrinogen(additive model:β^b（95%CI）=0.153（0.02-0.29）,P_adj=0.026)were significantly correlated.（6）In the additive,dominant and invisible models of genetic model,no RP11-386M24.6 single nucleotide rs17647695,rs28692833 and rs17704159polymorphisms were found to be correlated with C-reactive protein,homocysteine and uric acid levels in patients with IS phlegm and blood stasis syndrome,and the differences were not statistically significant(all P,P_adj>0.05).The RP11-386M24.6 single nucleotide rs28692833 polymorphism was correlated with C-reactive protein in patients with CHD phlegm and blood stasis syndrome(additive model:β^b（95%CI）=15.620（6.70-24.55）,P_adj=0.001;dominant model:β^b（95%CI）=14.110（3.08-25.15）,P_adj=0.013;recessive model:β^b（95%CI）=39.360（16.89-61.82）,P_adj=0.001)were significantly correlated.Conclusion:（1）The lncRNA RP11-386M24.6 single nucleotide polymorphism was not correlated with susceptibility to IS,CHD.（2）The lncRNA RP11-386M24.6 single nucleotide polymorphism may affect the lipid level and coagulation function in patients with IS and CHD phlegm and blood stasis syndrome,suggesting that RP11-386M24.6 may be a candidate therapeutic target for phlegm-stasis syndrome of IS and CHD.（3）The lncRNA RP11-386M24.6 single nucleotide polymorphism may be correlated with fasting glucose and uric acid levels in patients with CHD phlegm stasis.