Effect of ABCB1 3435C>T transporter gene polymorphism on plasma efavirenz concentration in HIV-1 infected Thai adults

Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=21)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was 0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=27)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Conclusions:There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB13435 T/T and ABCB13435 C/T genotypes.No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.

Relationship between polymorphisms of ABCB1 gene and epilepsy in Uygur population of Xinjiang region

Objective:To study the association of ABCB1 gene with epilepsy in the Uygur population of Xinjiang region.Methods: In this case-control study, 232 confirmed epilepsy patients from Xinjiang affiliated Medical University from January 2017 to June 2018, and 116 were recruited in the case group and 116 healthy individuals were selected as the control group. 2 mL of the blood sample was collected from each subject, from which the DNA was extracted. The polymorphism gene was determined by polymerase chain reaction followed by restriction fragment length polymorphism.Results: No significant association was observed in C3435T alleles and genotypes with epilepsy between the case and the control groups (P>0.05), G2677T/A genotypes with epilepsy was the same as GG in both of the groups.Conclusions:The polymorphisms of C3435T gene may not be associated with epilepsy in the Uygur population from the Xinjiang region.

Effects of the ABCB1 genetic polymorphism on vancomycin blood concentration in critically ill patients of Chinese

To investigate the clinical application of vancomycin blood concentration monitoring in critically ill patients and the influence of the ABCB1 gene polymorphism on vancomycin dnug concentrations to guide clinically rational usage of vancomycin.The vancomycin blood concentration monitoring data on 141 critically ill patients in our hospital from November 2016 to March 2017 were analyzed and 68 patients who received the same dosages of vancomycin were subjected to ABCB1 genotyping.The results showed that among the 141 critically ill patients,68(48.22%)showed sub-target concentrations of vancomycin,averaging 5.58±2.54μg/mL;29 patients(20.56%)had higher than target concentrations,with an average value of 33.01±9.38μg/mL;and 44 cases(31.21%)were in the normal concentration range,with an average of 14.72±2.75μg/mL.The vancomycin concentrations in 1236TT-genotype patients were significantly higher than those of the 1236CC and 1236CT-genotype patients.The concentrations in the 2677AA-genotype patients were significantly higher than those in the 2677AT,2677GA,2677GG and 2677GT patients.Vancomycin concentrations in 3435CT patients were significantly higher than those in 3435CC,but slightly lower than those in 3435TT patients.The ABCB11236C>T,2677G>T/A and 3435C>T gene mutations may affect vancomycin blood concentrations.At the same time,other factors such as gender,age,co-morbidities and other transporters possiblely play the roles in influencing the concentration of vancomycin in patients.All these factors finally cause individual differences.

Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters.Herein,we firstly provide the evidence that a nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase.Acute and chronic liver diseases with viral,metabolic and autoimmune etiology were excluded.Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance.Liver biopsy showed:Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment,Kupffer’s cell activation/hyperplasia and preserved biliary ducts.Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria,ATP8B1 and ABCB11 gene analysis was performed.Surprisingly,we found a novel nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygosis.The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance.Immunohistochemistry confirmed a significant reduction of mutated gene related protein(familial intrahepatic cholestasis 1).The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6th and 12th mo.CONCLUSION A genetic abnormality,different from those already known,could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition,thus encouraging further mutation detection in this field.

Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients

Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism （SNP） C3435T （rs1045642） affects the timing of co-translational folding and insertionof P-gp into the membrane,

ABCB1基因多态性对乳腺癌患者多西他赛血液学毒性的影响

目的探讨乳腺癌患者ABCB1(3435 T>C、2677 T>G)基因多态性对多西他赛血液学毒性作用的影响,旨在为临床安全用药提供参考。方法回顾性分析77例乳腺癌患者资料,根据化疗方案的不同分为两组:实验一组(多西他赛联合环磷酰胺)和实验二组(多西他赛联合表柔吡星)。应用六周期化疗方案,分析两组不同基因型对应患者出现骨髓抑制情况的差异。计数资料比较采用χ~2检验,P<0.05为差异有统计学意义。结果 ABCB1(3435T>C)野生纯合型(TT型)乳腺癌患者应用多西他赛发生血液学毒性的风险高于其他基因型,差异有统计学意义(P<0.05)。ABCB1(2677T>G)不同基因型患者发生血液学毒性风险的差异无统计学意义(P>0.05)。结论乳腺癌患者应用多西他赛时可以通过检测ABCB1(3435T>C)的基因型,在一定程度上可以预知患者的血液学毒性风险,从而调整患者治疗方案,实现多西他赛的个体化治疗。