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Distribution Of SLCO1B1 Genotypes In Lanzhou And Correlation Between Genotypes And Lipid Lowering Effects Of Statins

Posted on:2020-11-27Degree:MasterType:Thesis
Country:ChinaCandidate:H Y YanFull Text:PDF
GTID:2404330599955468Subject:Internal medicine
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ObjectiveThe purpose of this study is to explore the distribution characteristics of SLCO1B1 genotypes in Gansu,and to compare the distribution characteristics of other cities in China and Europe and America,to explore the distribution characteristics of SLCO1B1 genotypes;to compare the blood lipids,liver and kidney functions during the follow-up of different SLCO1B1 genotypes and statins The differences in creatine kinase and blood glucose levels,and the effects of genotypes on the lipid-lowering effects of statins and the safety of statins,and provide a reference for better application of statins in clinical work.MethodThe study was divided into two parts.The first part selected 386 patients who were admitted to the Department of Cardiology of Gansu Provincial People's Hospital from December 2016 to January 2018.The SLCO1B1 genotypes 388A>G and 521T>C sites were detected to investigate coronary heart disease in Gansu.The distribution of SLCO1B1 gene was different between the group and the control group;and compared with the distribution characteristics of other cities in China and other countries such as France,the United States,and Tanzania,the distribution characteristics of SLCO1B1 gene were explored.In the second part,patients taking coronary heart disease were treated with rosuvastatin 10 mg/day.The changes of blood lipid levels,creatine kinase,liver and kidney function blood glucose were measured in the first,third and sixth months after taking the drug,and the efficacy and safety of different SLCO1B1 genotypes and statins were explored.ResultThe frequencies of AA,AG and GG genotypes of C.388A>G locus in SLCO1B1 gene in Gansu were 5.44%,39.90% and 54.66%,respectively;the frequencies of alleles A and G were 25.39% and 74.61%,respectively;The frequencies of TT,TC,and CC genotypes in the 521T>C locus were 83.68%,15.03%,and 1.30%,respectively;the frequencies of the alleles T and C were 91.19% and 8.81%,respectively.The frequencies of SLCO1B1 genotypes 1a/1a,1a/1b,1b/1b,1a/15,1b/15,and 15/15 were 5.44%,35.75%,42.49%,4.15%,10.88%,and 1.30%,respectively.The frequencies of *1a,*1b,and *15 haploids were 25.39%,65.80%,and 8.81%,respectively.The genotypes,alleles,and haploid distribution frequencies in Gansu were compared with other places.The differences in AA,AG,and GG genotypes were significantly different from those in Chile,the United States,France,Finland,Thailand,Ethiopia,and Tanzania.The difference between the G allele and Chile,the United States,Ethiopia,and Tanzania was statistically significant.The differences between TT,TC,CC genotypes and Xinxiang City,Hanchuan City,Zhengzhou City,Finland,Russia,Brazil,France,Chile,Ethiopia,Tanzania were statistically significant;T,C alleles and Zhengzhou,Russia,Brazil,France,Ethiopia,Tanzania,the difference is statistically significant;*1a/1a,*1a/1b,*1b/1b,*1a/15,*1b/15,*15/15 genes and the Americas,Europe,Yunnan The differences between the Bai and China(Xiangya)were statistically significant.The difference between *1a,*1b,*15 haploid and Macedonia was statistically significant.Patients with coronary heart disease who were followed up with rosuvastatin 10 mg/day were compared with blood lipid levels,creatine kinase,liver and kidney function,and blood glucose levels at 1,3,and 6 months after discharge.They were compared with the admission level and found to be 1a/1a and 1a in January.The difference of HDL-C and LDL-C in /15 was statistically significant.The change of HDL-C was 1a/1a higher than 1a/15,the change of LDL-C was 1a/15 more than 1a/1a,and the 1a/1a and 1a/15 of June.The difference between HDL-C and LDL-C was statistically significant.The difference of LDL-C between 1a/1b and 1a/15 was statistically significant.There was a statistically significant difference in blood glucose changes between 1a/1a and 1a/1b in January.There was a statistically significant difference in serum creatinine between 1a/1a and 1a/15.There was a statistically significant difference in blood urea change between 1a/1b and 1a/15.,but the results are within the normal range.During the follow-up period,no myopathy events occurred in all genomic patients.Pearson correlation analysis between genotype and blood lipid levels revealed that LDL-C changes were associated with SLCO1B1 genotype.ConclusionThe SLCO1B1 gene in Gansu is mainly *1b/1b,followed by *1a/1b;the haploid is mainly *1b,followed by *1a;the C.388A>G site is dominated by GG genotype;C.521 T The >C locus is dominated by the TT genotype.There was no significant difference in genotype between the two groups in the coronary heart disease group and the control group.Compared with other regions of China and other countries such as the United States,Russia,France,etc.,the SLCO1B1 C.388A>G and SLCO1B1 C.521T>C locus genotypes are related to ethnicity.Sexuality and ethnic origin cause different genotypes and allele frequencies of SLCO1B1 C.388A>G,C.521T>C loci.There was a correlation between SLCO1B1 genotype and LDL-C,and the transport ability of *15 haploid to rostastatin was lower than that of *1a haploid and lower than *1b haploid,suggesting that SLCO1B1 C.521T>C Point mutations lead to a reduction in the amount of statin drug transport in the liver,and clinical attention should be paid to mutations in the C.521T>C site.During the follow-up period,there were no adverse reactions such as liver and kidney dysfunction and blood glucose fluctuation,but the mutation of C.521T>C site led to an increase in creatine kinase,which should be paid attention to in clinical practice.
Keywords/Search Tags:Gansu, gene polymorphism, rosuvastatin, SLCO1B1, efficacy, safety
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