ABSTRACT
OBJECTIVE:To investigate the effects of UGT1A6 and UGT1A9 gene polymorphisms on blood concentration of valproic acid in Han epileptic patients.METHODS:Totally 107 Chinese Han epileptic patients were selected from outpatient department of our hospital during Jan.2014-Apr.2015.They were given valproic acid monotherapy treatment for 3 months to 6 years.The steady state concentration ofvalproic acid was detected by EMIT.UGT1A6 (rs2070959,rs6759892) and UGT1A9 (rs13418420,rs2741045,rs2741049,rs6731242,rs72551330) genotypes were detected by MALDI-TOF-MS.The correlation of gene polymorphism with con centration dose ratios (CDR) of valproic acid was investigated.RESULTS:UGT1A9 rs72551330 mutation had not been detected,and the frequency of genotypes in other 6 sites were all in line with Hardy-Weinberg balance (P＞0.05).The CDR of valproic acid in pa tients with UGT1A6 rs2070959,rs6759892 mutation (AG+GG or TG+GG type) were significantly lower than those with wild homozy gote (AA or TT type),with statistical significance (P＜ 0.05).There was no statistical significance in CDR of valproic acid among patients with UGT1A9 rs13418420,rs2741045,rs2741049 and rs6731242 wild homozygote and mutation (P＞0.05).CONCLUSIONS:UGT1A6 rs2070959,rs6759892 gene polymorphisms of Han epileptic patients are associated with blood concentration of valproic acid,and the patients with UGT1A6 rs2070959,rs6759892 mutation need more dose ofvalproic acid.
ABSTRACT
Objective:To analyze the association between gene single nucleotide polymorphisms ( SNP) of methylenetetrahydrofo-late reductase ( MTHFR) gene and lower extremity atherosclerotic disease ( LEAD) . Methods:The clinical data and peripheral blood were collected from 384 participants (224 LEAD cases and 160 normal controls) from Han population of Minnan Fujian. LEAD was detected with ankle brachial index ( ABI) , toe brachial index ( TBI) , color Doppler ultrasonic examination and the other imaging stud-ies. The SNP genotypes including rs1801133, rs1801131, rs2274976, rs4846048, rs3737966, rs1537515, rs4846049, rs3834044, rs13306561 and rs3737964 in the MTHFR gene were detected by matrix-assisted laser desorption ionization-time of flight ( MALDI-TOF) . Results:The genotype distributions of the ten loci were in accordance with Hardy-Weinberg equilibrium. There were 37 obvi-ous linkage disequilibrium, including the association between rs4846048 and rs3737966 (D′>0. 9) and so on. There were significant differences (P=0. 02) in GCCTCGGAAT haplotypes of MTHFR gene groups between LEAD cases and the normal groups. The results from chi-square test of allele frequencies suggested rs1801131 (OR=1. 287),rs4846048 (OR=1. 844,P=0. 02), rs3737966(OR=1. 339),rs4846049 (OR=1. 314) and rs3737964 (OR=1. 522). Significant differences (P<0. 05) were observed between LEAD and the normal groups in Cochran- Armitage trend test and Dominant gene action test of rs4846048. Conclusion: The SNP of rs1801131,rs4846048,rs3737966,rs4846049 and rs3737964 might be associated with the susceptibility of LEAD,and rs4846048 gene mutation might serve as a risk factor for LEAD in the community-based population.
ABSTRACT
A method was developed for the determination of four sulfa antibiotics in groundwater, soil and excreta using solid phase micro extraction disks coupled with high performance liquid chromatography. The influence of eluent, different solid phase micro extraction membranes on the recovery of sulfa antibiotics in groundwater was investigated and it was found that when using the mixture of methyl alcohol and 1 . 0% formic acid as eluent, HLB ( divinyl benzene-N-vinyl pyrrolidone polymer ) as extraction membranes, an optimal enrichment effect was obtained. Different pretreatment methods for the 3 kinds of samples abovementioned were also examined. It was found that the signal response values obtained by using mixture of methyl alcohol and 1 . 0% formic acid as base solution of standard or sample solution was higher 8-10 times than that by using methyl alcohol only. Under the optimal conditions, good linear relationships were obtained in the sulfa antibiotics concentrations of 0 . 005-10 . 0 mg/L with the correlation coefficients>0 . 9999;The detection limits of sulfathiazole ( ST ) , sulfadiazine ( SM ) , sulfamethazine ( SM2 ) , sulfamethoxazole ( SMX ) were 1 . 08 , 3. 56, 4. 63 and 1. 84 ng/L(S/N=3), respectively. The enrichment factors for four sulfa antibiotics were 4000 times with solid phase micro extraction disks. The RSD of matrix spiked samples were 0. 1%-0. 4%(n=7). The proposed method was applied to the determination of the four sulfa antibiotics in groundwater, soil and excreta with spiked recoveries of the four sulfa antibiotics in the range of 69 . 80%-117 . 60%.