Screening and Evaluation of Gene Mutations in Familial Hypercholesterolemia Pedigrees in Guizhou Province
Objective:To explore the results of gene mutation screening and evaluation in familial hypercholesterolemia(FH)families in Guizhou Province.Methods:According to the diagnostic criteria of the Dutch Lipid Diagnostic Network(DLCN)guidelines,a patient diagnosed with FH was selected from a tertiary hospital in Guiyang City from November 2021 to November 2022 for study.The pedigree was analyzed,and the total cholesterol(TC),triglyceride(TG),LDL-C,and high-density lipoprotein cholesterol(HDL-C)levels of family members were detected by C8000 automatic biochemical analyzer.The clinical data and DNA of the family were collected,and the pathogenic genes were sequenced by whole genome exon sequencing.The single nucleotide polymorphism(SNP)sites of four FH-re-lated genes[low density lipoprotein receptor(LDLR),apolipoprotein B(ApoB),sibutramine 9a(PCSK9),LDLR adaptor protein 1(LDL-RAP1)]were screened out,and the pathogenicity of SNP sites was analyzed by Polyphen-2 and SIFT software.The incidence of cardio-vascular disease during dual filtration plasma exchange(DFPP)adsorption therapy and the changes in apolipoprotein A(ApoA),apolipoprotein E(ApoE),apolipoprotein B(ApoB),lipoprotein a(LPa),TC,TG,HDL-C,LDL-C,and free fatty acid(FFA)levels before and after treatment were also retrospectively analyzed.Results:The serum TC of Ⅰ-1,Ⅱ-1 and Ⅱ-2 members of the family was 8.91 mmol/L,8.12 mmol/L and 7.98 mmol/L,respectively.Ⅰ-1,Ⅱ-1 and Ⅱ-2 met the diagnostic criteria of FH.The scores of rs676210 and rs679899 in the ApoB gene of the family were 0.998 and 0.996,respectively,and the score of c.10094 A＞T was 0.795.SIFT software predicted that the above three sites were harmful.The patient's condition was stable after DFPP treatment,and no serious cardiovascular events oc-curred.Compared with before adsorption treatment,the levels of ApoA,ApoE,ApoB,LPa,TG,HDL-C,LDL-C and TC after adsorption treatment were lower than those before adsorption treatment,and the levels of FFA were higher than those before adsorption treatment.The difference was statistically significant(P＜0.05).Conclusion:Mutations in the two SNPs of the ApoB gene are likely to cause FH,and DFPP treatment is beneficial to regulate blood lipid levels in FH patients,thereby reducing the risk of cardiovascular disease.
万方数据
维普
