| PART Ⅰ:ESTABLISHMENT OF THE SAMPLE BANK OF FAMILIAL HYPERCHOLESTEROLEMIAFamilial hypercholesterolemia(FH)is a serious dominant metabolic disease.The cholesterol level of patients is significantly higher than that of normal people.It induces early arteriosclerosis(As)and even early death.At present,FH is widely concerned internationally,but China still lack of systematic research on it.Objective:Establish a FH sample bank in China and analyze the clinical characteristics to provide guidance for FH diagnosis and treatment in China.Methods:Use familial hypercholesterolemia screening and diagnosis and treatment of Chinese experts consensus screening criteria,select LDL-C≥ 4.65 mmol / L or take high-intensity statin LDL-C still ≥ 3.7mmol /L,the diagnosis using the(Dutch Lipid Clinical Network,DLCN),≥ 3points for patients diagnosed as FH positive;1.Sign the informed consent and fill out the questionnaire;2.Patients aged ≥16 years were in the adult group and <16 years old in the children group,and the two groups are divided according to the presence or absence of yellow tumors;3.Collect patient clinical medication data and follow up monthly;4.Collect patient serum and DNA samples and save them;5.Analyze the characteristics of blood lipids and imaging lesions at baseline;6.Use of Simon Broom,MEDPED,familial hypercholesterolemia screening and diagnosis and treatment of Chinese expert’s consensus standards and DLCN standards comparison,to explore the diagnostic detection rate and correct rate of FH patients in China;7.Analyze the patient’s first visit and follow-up for 3 months and above the current status of treatment and compliance rate;8.Analyze the data using the SPSS20.0 software package;Result:1.Collect 200 patients with FH,200 clinical data,168 serum and DNA samples,and initially establish a FH sample bank;2.In the adult group,the corneal arch of the patients with xanthomas,early onset ASCVD,peripheral vascular disease,stent surgery and coronary artery bypass grafting were significantly higher than those without xanthomas(P<0.05);3.Adults with axillary aortic valve,mitral valve,tricuspid regurgitation,aortic arch and aortic valve calcification,carotid intima cIMT thickness was significantly greater than / greater than no yellow tumor patients(p<0.05);4.Compared with the DLCN,the detection rates of children with FH in China using Simon Broom,MEDPED,and Chinese consensus diagnostic criteria were 92.54%,100%,and 16.42%,respectively;and the detection rate for adult FH patients was 89.47%.80.45%,64.66%,the correct rate was 90.5%,87%,48.7%.5.In the first visit of the child,67 cases were untreated,23 cases(17.29%)were treated by adult patients,and no treatment was reached.After 3months and above,50 children were treated and 14(20.89%)were up to standard.79 patients were treated and 4(3.01%)met the standard.Conclusion:1.Initially established a sample library of FH patients;2.In adults with yellow tumors,the cardiovascular changes are severe;3.The existing treatment of FH patients in China is seriously under-standard and should be standardized;4.Compared with the DLCN criteria,China’s expert consensus diagnosis standard diagnosis rate and correct rate are low,and need to be improved;PART Ⅱ: COMPARATIVE STUDY ON CLINICAL FEATURES OF SITOSTEROLEMIA AND FAMILIAL HYPERCHOLESTEROLEMIASitosterolemia(STSL)is a rare autosomal recessive disorder caused by mutations in the ABCG5/8 gene,which is currently reported in more than 100 cases worldwide.The clinical manifestations of the disease resemble HoFH,early onset of coronary heart disease,in addition to the patient’s serum phytosterols significantly increased.Laboratory gene sequencing revealed that there were 19 patients with ABCG5/8 gene mutation in the sample bank and compared it with HoFH.Objective:The relationship between the two diseases was analyzed in comparison with HoFH patients.Method:1.Targeted capture second-generation sequencing to detect gene mutations;2.Biochemical tests TC,LDL-C,HDL-C,TG;blood test,fresh blood smear;imaging examination of cardiovascular disease;3.Gas chromatography for the detection of phytosterols(mainly including sitosterol,stigmasterol and campesterol)and the absorption marker dihydrocholesterol,synthetic markers(squalene,dehydrocholesterol,7-cholesterol);4.Analyze data using the SPSS20.0 software package;Result:1.20 patients with sitosterolemia,all with ABCG5/8 homozygous or complex heterozygous mutations;2.Compared with HoFH patients,TC,LDL-C was significantly lower(P<0.05)and HDL-C was significantly higher in STSL patients(p<0.05).There was no statistical difference in the four lipids of ABCG5/8 gene mutation in STSL patients(P<0.05);3.There were no significant differences in the imaging examination between the two groups(P>0.05).4.The level of plant sterols were significantly elevated in STSL patients compared with HoFH patients(P < 0.001);5.The volume of STSL platelets,distribution width,compressive volume and large platelet ratio of STSL were significantly higher than those of HoFH patients(P<0.05).Some patients with STSL showed oral erythrocytosis and giant platelets in blood smears,and no abnormalities in blood smears in HoFH patients.6.The TC,LDL-C of the two groups were significantly decreased after treatment(P<0.05),and the decrease of TC and LDL-C was higher in STSL patients(P<0.05).Conclusion:1.STSL and HoFH patients have similar clinical manifestations,but different genetic patterns,and their serum phytosterols are significantly higher than HoFH patients;2.STSL patients can effectively control serum cholesterol lowering serum cholesterol levels through therapeutic lifestyle interventions and ezetimibe or statin therapy;... |
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