AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: ...AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.展开更多
免疫印迹显示,抗牛精子sp18族膜蛋白的单克隆抗体(sp18单抗)与小鼠精子14,18,22,30和60 ku 5条带有较弱的抗原信号,同时,sp18单抗也能结合鸡卵溶菌酶。间接免疫荧光证实小鼠精子头后部存在sp18抗原。获能2h的小鼠精子与0.182 mg/mL的s...免疫印迹显示,抗牛精子sp18族膜蛋白的单克隆抗体(sp18单抗)与小鼠精子14,18,22,30和60 ku 5条带有较弱的抗原信号,同时,sp18单抗也能结合鸡卵溶菌酶。间接免疫荧光证实小鼠精子头后部存在sp18抗原。获能2h的小鼠精子与0.182 mg/mL的sp18单抗共孵育15~20min后进行体外受精,结果发现,单抗组的受精率(77.1%)与血清对照组(79.2%)和空白对照组(80.3%)间无显著差异(p>0.05)。继续培养受精卵发现,3组胚胎发育至2-细胞期的比率分别为100%,100%和97.9%(p>0.05);发育至4-细胞期的比率分别为0,64.1%和64.3%,即单抗组胚胎的发育被完全阻断在2-细胞期(p<0.001)。0.5%链霉蛋白酶消化除去阻断胚胎的透明带后,间接荧光定位发现,2个胚胎细胞表面均存在sp18抗原。0.182mg/mL的sp18单抗与体内受精的胚胎共培养时,胚胎发育至2-细胞期(95.2%vs 92.9%)和4-细胞期(70.5 % vs 77.9%)的比例与对照组无显著差异(p>0.05)。结果表明,小鼠精子sp18族膜蛋白在受精时掺入卵母细胞质膜系统,成为胚胎细胞表面具有功能的质膜成分,与突破胚胎发育的2-细胞期阻断现象有关。展开更多
In the present study, we aimed to investigate the effect of CYP3A4* 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotypin...In the present study, we aimed to investigate the effect of CYP3A4* 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A pharmacokinetic study was then carried out in three groups with CYP3A4*1/*1 (n = 6), CYP3A4*1/*18 (n = 6) and CYP3A4*18/*18 (n = 6) genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups (P〈0.05). Compared with the CYP3A4*1/*1 group, the Cm,x of zolpidem in *1/*18 and *18/*18 groups (mean, 95% CI) was 0.89 (0.65-1.12) and 0.57 (0.47-0.66), respectively, and the AUC0-1 in the *1/*18 and *18/*18 groups (mean, 95% CI) was 0.74 (0.22-1.26) and 0.61 (0.24-0.98), respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A* 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4* 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.展开更多
文摘AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.
文摘免疫印迹显示,抗牛精子sp18族膜蛋白的单克隆抗体(sp18单抗)与小鼠精子14,18,22,30和60 ku 5条带有较弱的抗原信号,同时,sp18单抗也能结合鸡卵溶菌酶。间接免疫荧光证实小鼠精子头后部存在sp18抗原。获能2h的小鼠精子与0.182 mg/mL的sp18单抗共孵育15~20min后进行体外受精,结果发现,单抗组的受精率(77.1%)与血清对照组(79.2%)和空白对照组(80.3%)间无显著差异(p>0.05)。继续培养受精卵发现,3组胚胎发育至2-细胞期的比率分别为100%,100%和97.9%(p>0.05);发育至4-细胞期的比率分别为0,64.1%和64.3%,即单抗组胚胎的发育被完全阻断在2-细胞期(p<0.001)。0.5%链霉蛋白酶消化除去阻断胚胎的透明带后,间接荧光定位发现,2个胚胎细胞表面均存在sp18抗原。0.182mg/mL的sp18单抗与体内受精的胚胎共培养时,胚胎发育至2-细胞期(95.2%vs 92.9%)和4-细胞期(70.5 % vs 77.9%)的比例与对照组无显著差异(p>0.05)。结果表明,小鼠精子sp18族膜蛋白在受精时掺入卵母细胞质膜系统,成为胚胎细胞表面具有功能的质膜成分,与突破胚胎发育的2-细胞期阻断现象有关。
基金Funds of the Chinese Army Medical Science and Technology Research"Eleventh Five-Year Plan"Project(Grant No.06G023)
文摘In the present study, we aimed to investigate the effect of CYP3A4* 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A pharmacokinetic study was then carried out in three groups with CYP3A4*1/*1 (n = 6), CYP3A4*1/*18 (n = 6) and CYP3A4*18/*18 (n = 6) genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups (P〈0.05). Compared with the CYP3A4*1/*1 group, the Cm,x of zolpidem in *1/*18 and *18/*18 groups (mean, 95% CI) was 0.89 (0.65-1.12) and 0.57 (0.47-0.66), respectively, and the AUC0-1 in the *1/*18 and *18/*18 groups (mean, 95% CI) was 0.74 (0.22-1.26) and 0.61 (0.24-0.98), respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A* 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4* 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.