The Gene Polymorphism Of SLCOIBI And Its Correlation With Resuvastatin Lipid-lowering Efficacy And Safety In Kunming Han Population

Objective:The purpose of this study was to analyze the distribution SLCO1B1 gene polymorphism in Kunming Han population,and compare with the north and the south city in China,Europe,America,Africa,Asia and other countries,in order to further understand the characteristics of the distribution SLCO1B1 gene in Kunming Han population According to SLCO1B1 gene polymorphism and its encoding OATP1B1 function and pharmacology of statins,evaluate Rosuvastatin lipid-lowering efficacy and related side effects,in order to guide the clinical work type and dose of choice provide theoretical guidance for statins individualized medication.Methods:Choice in February 2017-June 2017 in the second affiliated hospital of Kunming medical university of cardiology admission taking statins therapy and 436 patients with unrelated relation in Kunming area,the application of PCR fluorescent probe method to detect SLCO1B1 gene in patients with c.388 A>G locus,c.521 T>C locus gene fragments,analyzing SLCOIBI gene distribution in Kunming Han population,and comparing with the north and the south city in China,Europe,the America,Africa,Asia and other countries.Taking Rosuvastatin daily track 10 mg patients were followed up for 6 months(August 2017-December 2017),select eligible 98 patients according to genotype was divided into wild group and mutant group,observe the lipid-lowering effects of statins and the related side effects.Results:1.The distribution of SLCOIBI genetic polymorphism c.388A>G locus in Kunming Han population.(1)The frequency of SLCOIBI gene c.388A>G locus allele AA,AG,GG respectively were 5.96%,37.16%and 5.96%,the SLCO1B1 gene c.388A>G locus allele in Kunming Han population was mainly mutant allele GG.the frequency of those alleles in men were:6.73%,34.08%,59.19%,and the frequency of those alleles in women were:5.16%,40.38%,54.46%,three alleles no statistical difference between different genders(P>0.05);(2)The frequency of SLCOIBI gene c.388 A>G locus allele in this research had no statistical difference with Dali,Zhengzhou,Beijing,Guangzhou,Changsha,Nanchang,Changsha1,Beijing1(P>0.05),had statistical difference with Hunan(P =0.003)and Rome(P<0.001),Hungary(P<0.001),Finland(P<0.001),(P<0.001),Greece,Albania(P<0.001),France(P<0.001),Europe(P<0.001),Macedonia(P<0.001),the United States(P<0.001),Washington(P<0.001),Tanzania(P<0.001),Pakistan(P<0.001),the SLCOIBI gene c.388A>G locus gene polymorphism was similar with the north and the south city in China,but different with Europe,America,Africa,Asia and other countries,which wild allele AA was significantly higher than that in Kunming Han population.2.The distribution of SLCOIBI genetic polymorphism c.521T>C locus in Kunming Han population.(1)The frequency of SLCOIBI gene c.521 T>C locus alleles TT,TC,CC respectively were:81.65%,17.66%,0.69%,the SLCOIBI gene c.388A>G locus allele in Kunming Han population was mainly wild allele TT,the frequency of those alleles in men were:82.16%,16.9%,0.94%,and the frequency of those alleles in men were:81.17%,18.38%s 0.45%,three alleles no statistical difference between different genders(P>0.05);(2)The frequency of SLCO1B1 gene c.521 T>C locus allele in this research had no statistical difference with Guangzhou,Changsha,Hunan,Nanchang,Changsha,Beijing,Beijing 1,Albania,the United States(P>0.05),had statistical difference with Dali(P = 0.046),Guangdong(P = 0.036),Zhengzhou(P<0.001)and Rome(P<0.001),Hungary(P<0.001),Finland(P<0.001),Greece(P<0.001),France(P<0.001),Europe(P<0.001),Macedonia(P<0.001),Washington(P<0.001),Pakistan(P<0.001),Tanzania(P<0.001),the SLCOIBI gene c.388A>G locus gene polymorphism was similar with the north and the south city in China,and different with Dali,Zhengzhou,with Europe,Americas,Africa,Asia and other countries,which wild allele TT was significantly lower than that in Kunming Han population.3.The distribution of SLCO1B1 genetic polymorphism in Kunming Han population.The frequency of SLCO1B1 genotype*la/*la,*la/*lb,*la/*15,*lb/*lb,*lb/*l5,*15/*15 respectively were:6.19%,31.42%,4.82%,44.0%,12.84%,0.69%,the distribution of SLCOIBI gene had polymorphic in Kunming Han population:with mainly mutant homozygote*lb/*lb,the frequency of those genotype in men were:5.63%,34.27%,4.69%,42.25%,12.21%,0.94%,the frequency of those genotype in women were:6.73%,28.70%,4.93%,45.74%,13.45%,0.45%,6 kinds of genotype had no statistical difference between different gender(P>0.05),The genotype with*5 was not detected.,such as:*la/5,*lb/*5,*5/*5,*l5/*5.4.The SLCO1B1 gene polymorphism and Resuvastatin lipid-lowering efficacy and safety.(1)In second part of this research selected 98 patients,wild groups 8 patients(8.08%),mutation group 90 patients(91.92%),including*la/*lb 33 patients,*la/*l5 2patients,*lb/*lb 37 patients,*lb/*15 18patients.This research followed up for 6 months,observed the TC,TG,LDL,HDL,NHDL,apoB,apoA1,LP(a),the changes of wild group and mutant group comparison,the above indexes had no statistical difference(P>0.05).There was no statistical difference Between the mutant three groups(P>0.05).There was no statistical difference between the mutant groups,*la/*lb and*lb/*lb(P>0.05).The comparison between*la/*lb group and*lb/*15 group was statistical difference in TC(P=0.015),LDL(P=0.013),NHDL(P=0.022),and apoB(P=0.044),which no statistical difference in TG,HDL,apoAl,and LP(a)(P>0.05).The comparison between*1b/*1b group and*lb/*15group was statistical difference in TC(P= 0.037),LDL(P= 0.013),NHDL(P=0.021),and apoB(P=0.034),which no statistical difference in TG,HDL,apoA1,LP(a)(P>0.05),the lipid-reducing effects with*15 alleles was reduced,and other alleles was no significant difference in the lipid-reducing effects.(2)In this research dad no statistical difference in liver function(ALT,AST),renal function(Cr),muscle enzyme(CK,CKMB)(P>0.05),and no symptoms such as myalgia in the medical history.Conclusion:1.The distribution of SLCO1B1 gene c.388A>G locus dad polymorphic in Kunming Han population.(1)The SLCO1B1 gene c.388A>G locus allele was mainly mutant allele GG in Kunming Han population.(2)There was no statistical difference between male and female genders of SLCO1B1 gene c.388A>G locus gene polymorphism in Kunming Han population.(3)The SLCO1B1 gene c.388A>G locus gene polymorphism was similar with the north and the south city in China,but different with Europe,America,Africa,Asia and other countries,which wild allele AA was significantly higher than that in Kunming Han population.2.The distribution of SLCOIBI gene c.521T>C locus dad polymorphic in Kunming region.(1)The SLCO1B1 gene c.521T>C locus allele was mainly mutant allele TT in Kunming Han population;(2)There was no statistical difference between male and female genders of SLCO1B1 gene c.521T>C locus gene polymorphism in Kunming Han population.(3)The SLCO1B1 gene c.388A>G locus gene polymorphism was similar with the north and the south city in China,and different with Dali,Zhengzhou,with Europe,Americas,Africa,Asia and other countries,which wild allele TT was significantly lower than that in Kunming Han population.3.The distribution of SLCOIB1 gene had polymorphic in Kunming Han population:with mainly mutant homozygote*1 b/*1 b,failed to detect with the*5 genotypes,such as:*la/*5,*lb/*5,*5/*5,*15/*5 and*15/a*15 was detected also fewer,with 3 patients and the composition ratio was 0.69%.4.The SLCO IB1 gene polymorphism and Resuvastatin lipid-lowering efficacy and safety.(1)effectiveness:The lipid-reducing effects with*15 alleles was reduced,and other alleles was no significant difference in the lipid-reducing effects.(2)safety:There was no significant correlation between the polymorphism of SLCO1B1 gene and the treatment safety of Resuvastatin 10mg.