Correlation Study Between Glucocorticoid Receptor Gene And Cerebral Small Vessel Disease

Objectives Metabolism syndrome may be one of the risk factors of cerebral small vessel disease(CSVD).It is suggested that two tag SNPs including rs7701443 and rs2963156 in glucocorticoid receptor gene(NR3C1)are related to the risk of metabolism syndrome.In the analysis of single genetic locus,compared with the GG and CC,the single nucleotide polymorphism(SNP)in CT?CT/TT of rs7701443 and rs2963156 individually increases the risk of metabolism syndrome.According to another research,in rs7701443 some indicators is increased in the AA subjects compared with GG+GA subjects,including body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),total cholesterol(TC)and low density lipoprotein-cholesterol(LDL-C)and that in rs2963156,the waist-to-hip ratio,glucose(GLU),TC,triglyceride(TG)and LDL-C is decreased in the TT subjects compared with CC+CT subjects.The risk factors of CSVD may consist of the risk factors of metabolism syndrome,body mass index,systolic blood pressure,diastolic blood pressure,waist-to-hip ratio and glucose.The study aims at discussing the relationship between the two SNPs rs7701443,rs2963156 in NR3C1 gene and CSVD.Methods Using prospective study,300 patients diagnosed as CSVD verified by cranial MRI were marked as case group,and 100 healthy participants with normal cranial MRI were classified as control group.The clinical data of all the participators:ages,genders,histories of hypertension,diabetes,hyperlipidemia and coronary atherosclerosis,years of education,serum total cholesterol,LDL-C,homocysteine,C reactive protein,GLU were collected.The SNPs of rs7701443 and rs2963156 in NR3C1 were detected by polymerase chain reaction(PCR),RCR-RFLP and Sequenom system.And then we calculate the frequency of two gene types and allelic genes individually by gene counting method.The cognition of the case groups and the control groups was evaluated by Montreal Cognitive Assessment scale(MoCA)and the correlation between the clinical data related to CSVD was analysed.Results 1 By comparing demographics and clinical indexes,it was concluded that there were apparent differences between the case groups and the control groups in ages(t=5.523,P<0.001),hypertension(?~2=13.505,P<0.001),diabetes(?~2=6.000,P=0.014),coronary atherosclerosis(?~2=6.214,P=0.013),homocysteine(t=1.989,P=0.048).2 Logistic regression correction results showed that there are significant differences between the case groups and the control groups in ages(OR:1.082;95%CI:1.048~1.118;P=0.000),hypertension(OR:2.521;95%CI:1.530~4.154;P=0.000),diabetes(OR:2.316;95%CI:1.167~4.594;P=0.016),coronary atherosclerosis(OR:2.698;95%CI:1.207~6.029;P=0.016).3According to Montreal Cognitive Assessment scale,visual space execution capability(Z=-2.74,P=0.01),nomination(Z=-2.24,P=0.02),abstract(Z=-2.46,P=0.01)and delayed memory(Z=-3.78,P=0.00)were significantly lower than the control groups.4 There was a polymorphism in rs7701443 from A to G.They were AA AG GG,of which the frequency were 16%,48.5%,35.5%in case groups and 12%,43%,45%in control groups.The frequency of AA,AG in case groups were higher than control groups,but there is no significant difference between them P=0.111).5 There was a polymorphism in rs2963156from T to C(TT CT CC respectly),of which the frequency were 1.0%,25.5%,73.5%in case groups and1.0%,19%,80%in control groups.The frequency of CT in case groups were higher than control groups,but without reaching a significant level(P=0.21).6 After the exclusion of CSVD patients over 80 years old,various possible grouping analysis was carried out for age:rs7701443 gene was found to have no correlation with age segmentation(P=0.072).There was no correlation between rs2963156 and age subsection(P=0.205).7Through the independent risk factors of CSVD,high blood pressure,diabetes,coronary heart disease illness interference in the case group and the control group separately as selection criteria,the three diseases history since then on the basis of comparing various genotypes,group rs7701443 in hypertension,diabetes,coronary heart disease group in the case group and the control group by fisher's exact test to compare the P values obtained are:P=0.408,P=0.726,P=0.0642,no significant difference.In the rs2963156 group,the values of P obtained by fisher's exact test were:P=0.3104,P=0.2904,P=0.2457 in the hypertension group,diabetes group,coronary heart disease group and control group,without significant difference.Conclusions 1 Ages,hypertension,diabetes,coronary atherosclerosis may be the independent risk factors of CSVD.2 CSVD may lead to recognition disorder which is frequently noted clinically in visual space execution capability,nomination,abstract and delayed memory.3 There is no correlation between the SNP of rs7701443 and rs2963156 in NR3C1.Figure 5;Table 23;Reference 102...