Phase I/II enzyme gene polymorphisms and esophageal cancer risk: A meta-analysis of the literature

AIM:Phase I/II enzymes metabolize environmental carcinogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations. METHODS: Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 Rsal polymorphisms, GSTM1 null type, GSTT1 null type and GSTP1 Ilel04Val. All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygous-non-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1, A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity. RESULTS: Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs (95%CI) compared with lie/lie of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters. CONCLUSION: A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.

Role of the Pentanucleotide (tttta)_n Polymorphisms of CYP11αGene in the Pathogenesis of Hyperandrogenism in Chinese Women with PolycysticOvary Syndrome

Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11α (tttta) n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11α (tttta) n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11α gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta) n of gene CYP11α exists in Chinese women and the polymorphism of CYP11α gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.

Polymorphisms in CYP2R1 Gene Associated with Serum Vitamin D Levels and Status in a Chinese Rural Population

Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.

Associations of Polymorphisms of the <i>CYP</i>1<i>A</i>1 and <i>CYP</i>1<i>B</i>1 Cytochrome P450 Genes with Breast Cancer in Kazakhstan

Associations of polymorphisms in rs4646903 site of CYP1A1 and rs1056836 site of CYP1B1 genes with the breast cancer (BC) were studied in two main ethnic groups of Kazakhstan Republic (Kazakhs and Russians). Total number of BC patients was 181, controls—397. The statistically significant differences were revealed in allele frequencies (χ2 = 5.93, р = 0.004) and in genotypes distribution (χ2 = 8.71, р = 0.015) in rs4646903 site of CYP1A1 gene in Kazakh but not in Russian group. The study of CYP1В1 rs1056836 site demonstrated differences in genotype distributions (χ2 = 7.48, р = 0.023) between BC patients and controls in Russian but not in Kazakh ethnic group.

Genetic Polymorphisms of CYP2C9: Comparison of Prevalence in the Lebanese Population with Other Populations

Background: There is little knowledge about genotyping of cytochrome P450s in the Middle East, and there has not been any report on the genotype of CYP 2C9 allelic variants in Lebanese population. Aims and objectives: The purpose of the study was to determine and compare the frequencies of the cytochrome P450 CYP2C9 variants in the Lebanese population with the frequencies in other ethnic populations. Methods: CYP2C9 genotypes were determined in a total of 146 samples of unrelated, healthy Lebanese individuals residing in different areas in Lebanon. Following DNA extraction from buccal cells and polymerase chain reaction, genotyping was performed by Pyrosequencing method. CYP2C9 genotypes results were compared to other populations;i.e., Middle Easterns, Europeans, Asians, and African Americans. Results and discussion: The frequencies of the CYP2C29*2, CYP2C9*3, and CYP2C9*4 alleles were 11.305%, 11.645%, and 1.025% respectively. No CYP2C9*5 allele variants were found among the Lebanese study sample. Vol- unteers could be divided into three CYP2C9 genotype groups: subjects (76.71%) with no mutated alleles (CYP 2C9*1*1;homozygous extensive metabolizers, EM), 21.23% with one mutated allele (CYP 2C9*1*2, *1*3, *1*4, and *1*5;heterozygous intermediate metabolizers IM), and 2.06% with two mutated alleles, homozygous variants as poor metabolizers, PM). The comparative analysis using genotype groups of different populations showed differences among Leba- nese and other Caucasians. Conclusion: This is the first report from Lebanon on CYP2C9 variants;it highlights a higher frequency of CYP2C9 extensive metabolizers compared to other populations including Caucasians. The results serve as a database on CYP 2C9 polymorphisms and baseline clinical data for dosing and avoiding adverse drug reac- tions of drugs metabolised by CYP2C9 in Lebanese patients.

Correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis

Objective:To study the correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis.Methods:A total of 80 patients who were diagnosed with viral myocarditis in Dongguan Branch, Yan'an University Affiliated Hospital between September 2014 and September 2017 were selected as the VMC group of the research, and 100 healthy volunteers who received physical examination in Dongguan Branch, Yan'an University Affiliated Hospital during the same period were selected as the control group of the research. The peripheral blood was collected to determine the IL-17A gene rs2275913 locus polymorphism, and serum was collected to determine the contents of myocardial injury and MMPs/TIMPs indexes.Results: The proportion of IL-17A gene GG genotype of VMC group was lower than that of control group and the proportion of GA+AA genotype was higher than that of control group;serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of VMC group were significantly higher than those of control group, and serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of patients with GA+AA genotype in VMC group were higher than those of patients with GG genotype.Conclusion: The mutation of the allele G to A in the peripheral blood IL-17A gene rs2275913 locus of patients with viral myocarditis can aggravate myocardial injury and MMPs/TIMPs imbalance.

Increased Risk of Acute Myeloid Leukemia in Patients with CYP1A1 Polymorphisms

Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.

CYP2E1 RsaⅠpolymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking

AIM： To investigate associations between the Rsa I polymorphism of CYP2E1 and risk of colorectal cancer. METHODS： A case-control study was conducted with 315 colorectal cancer cases （105 colon, 210 rectal） and 439 population-based controls in Jiangsu Province of China. Genomic DNA samples were assayed for restriction fragment length polymorphisms in CYP2E1 by PCR amplification followed by digestion with Rsa I. Information on smoking and alcohol drinking was collected using a questionnaire. Odds ratios （ORs） were estimated with an unconditional logistic model. RESULTS： The proportional distribution of the CYP2E1 Rsa I c1/c1, c1/c2 and c2/c2 genotypes were 61.4%, 35.6% and 3.0% in controls, 60.6%, 33.7% and 5.8% in colon cancer cases, and 58.4%, 34.0% and 7.7% in rectal cancer cases, respectively. A significant differencewas noted between controls and rectal cancer cases （P = 0.029）, the c2/c2 genotype being associated with elevated OR （adjusted age, sex and status of the smoking and alcohol drinking） for rectal cancer （1.64, 95% CI, 1.12-2.41, vs cl allele carriers）, but not for colon cancer. In interaction analysis between the CYP2E1 Rsa I genotype and smoking and drinking habits, we found a significant cooperative action between the c2/c2 genotype and alcohol drinking in the sex-, age-adjusted ORs for both colon （4.74, 95% CI, 1.10-20.40） and rectal （5.75, 95% CI, 1.65-20.05） cancers. Among nonsmokers, the CYP2E1 Rsa I c2/c2 genotype was also associated with elevated ORs in the two sites （1.95, 95% CI, 0.99-3.86 and 2.30, 95% CI, 1.32-3.99）. CONCLUSION： The results of the present study suggest that the CYP2E1 c2/c2 genotype increases susceptibility to rectal cancer and the gene-environmental interactions between the CYP2E1 polymorphism and smoking or alcohol drinking exist for colorectal neoplasia in general.

Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast cancer

Objective:To investigate the relationship between CYPIA1 genetic polymorphisms and the invasion and metastasis of breast cancer.Methods:The CYP1A1 gene polymorphism(an T-C transversion at nucleotide position 3801)was detected by the polymerase chain reaction and restriction fragment length polymorphism in 80 cases with breast cancer and 60 samples of normal breast tissue.The difference in genotypic distribution frequency between the groups,the correlation between the genotypes and the factors related to prognosis were analyzed.Results:The incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group(P=0.746).The proportion of variant genotype increased as clinical stage(P=0.006)advanced,as well as with increased numbers of lymph node metastases(P=0.010).Conclusions:In patients with breast cancer there is a correlation between the CYP1A1 CC allele and some factors indicating poor prognosis,including more lymph node metastases as well as a more advanced clinical stage.

Influence of CYP3A5 polymorphism on tacrolimus blood concentrations in renal transplant patients

Objective Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variation in its pharmacokinetics.Tacrolimus is a substrate of cytochrome P450(CYP)3A5.The aim of this study was to evaluate whether the A6986G polymorphism is associated with tacrolimus concentration/dose ratio.Methods Fifty-two Chinese renal transplant patients were enrolled in this study.Their body weight,dosage and concentration of tacrolimus were observed.CYP3A5 genotype was determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis.Results A significant association was found between tacrolimus levels per dose/kg/d and CYP3A5 gene A6986G polymorphism(P<0.001).The CYP3A5*3*3 patients have a significantly higher tacrolimus level/dose than CYP3A5*1*1 and CYP3A5*1*3.Conclusions CYP3A5 gene A6986G polymorphism is associated with tacrolimus pharmacokinetics and dose requirements.Pharmacogenetic methods could be employed prospectively to help the dose selection and to individualize immunosuppressive therapy according to the result.

Correlation between single nucleotide polymorphisms of 17β-HSD-1 and endometrial adenocarcinoma

Objective: To investigate the correlation between 17-beta-hydroxysteroid dehydrogenase type1(17β-HSD-1) gene polymorphisms and risk of endometrial adenocarcino-ma.Methods: Forty-one patients with endometrial adenocarcinoma were selected as experimen-tal group and twenty-seven healthy women were selected as control group.The three common single nucleotide polymorphism of 17β-HSD-1 gene at sites + 1004,+ 1322 and + 1954 were detected by allele-specific PCR(ASA-PCR).The allele frequencies were analyzed by SPSS13.0 software between endometrial cancer cases and controls.Results: We observed no significant difference in various frequency distribution between experimental group and control group.P1004= 0.994,P1322 = 0.974,and P1954 = 0.981.Conclusion: We found that three common SNPs with the 17β-HSD-1 gene were not associated with endometrial adenocarcinoma.We suggest that more research for 17β-HSD needs to explore.

Mutations in Exons of the CYP17-Ⅱ Gene Affect Sex Steroid Concentration in Male Japanese Flounder(Paralichthys olivaceus)

As a specific gene of fish,cytochrome P450c17-Ⅱ(CYP17-Ⅱ) gene plays a key role in the growth,development and reproduction level of fish.In this study,the single-stranded conformational polymorphism(SSCP) technique was used to characterize polymorphisms within the coding region of CYP17-Ⅱ gene in a population of 75 male Japanese flounder(Paralichthys olivaceus).Three single nucleotide polymorphisms(SNPs) were identified in CYP17-Ⅱ gene of Japanese flounder.They were c.G594A(p.G188R),c.G939A and c.G1502A(p.G490D).SNP1(c.G594A),located in exon 4 of CYP17-Ⅱ gene,was significantly associated with gonadosomatic index(GSI).Individuals with genotype GG of SNP1 had significantly lower GSI(P < 0.05) than those with geno-type AA or AG.SNP2(c.G939A) located at the CpG island of CYP17-Ⅱ gene.The mutation changed the methylation of exon 6.Indi-viduals with genotype AA of SNP2 had significantly lower serum testosterone(T) level and hepatosomatic index(HSI) compared to those with genotype GG.The results suggested that SNP2 could influence the reproductive endocrine of male Japanese flounder.How-ever,the SNP3(c.G1502A) located in exon 9 did not affect the four measured reproductive traits.This study showed that CYP17-Ⅱ gene could be a potentially useful candidate gene for the research of genetic breeding and physiological aspects of Japanese flounder.

Genetic biomarkers for hepatocellular cancer risk in a caucasian population

AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma(HCC)susceptibility in Caucasians. METHODS The present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two,independent,HCC-free,age/sex-matched control groups.The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation.The first control group comprised167 patients that were matched to the HCC cohort for the percentage of hepatitis B(HBV)and/or hepatitis C(HCV)infections.A second control group included192 virus-free,healthy individuals that were used to evaluate the generalizability of the identified predictive markers.All cases and controls were Caucasian.The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways.The study end-point was to assess the association between genetic variants and HCC onset. RESULTS Five genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV.According to a dominant model,reduced HCC risk was associated with three polymorphisms:ERCC1rs3212986(OR=0.46,95%CI:0.30-0.71,P=0.0005),GST-P1 rs1138272(OR=0.41,95%CI:0.21-0.81,P=0.0097),and CYP17A1 rs743572(OR=0.50,95%CI:0.31-0.79,P=0.0032).Conversely,according to a recessive model,increased HCC risk was associated with two polymorphisms:XRCC3 rs1799794(OR=3.70,95%CI:1.02-13.39,P=0.0461)and ABCB1 rs1128503(OR=2.06,95%CI:1.18-3.61,P=0.0111).These associations remained significant in a subgroup analysis,where patients were stratified according to viral status(HBV-or HCV-positive serology).Two variants exhibited a serology-specific effect:ABCB1 rs1128503(OR=4.18,95%CI:1.55-11.29,P=0.0048)showed an effect in the HBV-positive subgroup;and ERCC1 rs3212986(OR=0.33,95%CI:0.18-0.60,P=0.0003)showed an effect in the HCV-positive subgroup.Among the five markers identified,ERCC1 rs3212986(OR=0.43,P<0.0001)and CYP17A1 rs743572(OR=0.73,P=0.0310)had a different distribution in patients with HCC compared to healthy individuals.With a recursive partitioning approach,we also demonstrated that significant gene-gene interactions between ERCC1rs3212986,CYP17A1 rs743572,GST-P1 rs1138272,and the previously described UGT1A7*3 predictive marker,played a role in the complex trait of HCC susceptibility.CONCLUSION We identified five polymorphisms and interactions that contributed crucially to predicting HCC risk.These findings represented an important step towards improving HCC diagnosis and management.

IL-17A基因rs8193037和rs8193038位点多态性与川崎病的关联性

目的:了解IL-17A基因rs8193037及rs8193038位点多态性与川崎病的相关性。方法:纳入川崎病患儿及健康儿童各100例,应用聚合酶链式反应(polymerase chain reaction,PCR)和DNA直接测序法检测2组IL-17A基因rs8193037及rs8193038的单核苷酸基因多态性,比较2组目标等位基因频率的分布情况。结果:对于IL-17A基因rs8193037位点,川崎病组中GG、GA、AA基因型频率为70%、27%、3%,G、A等位基因分布频率分别为83.5%、16.5%;健康对照组GG、GA、AA基因型频率为72%、26%、2%,G、A等位基因分布频率分别为85%、15%,2组差异无统计学意义(χ^(2)=0.17,P>0.05)。对于IL-17A基因rs8193038位点:川崎病组GG、GA、AA基因型频率结果为72%、25%、3%,G、A等位基因分布频率为84.1%、15.9%;健康对照组中GG、GA、AA基因型频率结果为72%、26%、2%,G、A等位基因分布频率为84.6%、15.4%,2组差异无统计学意义(χ^(2)=0.01,P>0.05)。结论:IL-17A基因中rs8193037及rs8193038位点多态性与川崎病无明显关联性。

白细胞介素-17家族及其基因多态性与银屑病的研究进展

银屑病的具体发病机制尚不清楚。目前认为,白细胞介素-17(IL-17)参与的炎症级联反应等与银屑病发展有关。针对IL-17的靶向药物在银屑病治疗中有一定效果,但也存在不良反应,且不同个体存在疗效差异。近年来,随着基因多态性相关研究的逐渐深入,IL-17基因多态性与银屑病的遗传易感性之间的关系被广泛研究。目前全球已开展了针对多人群的IL-17基因与银屑病患病风险密切相关的全基因组关联研究,并针对不同个体对已批准生物制剂的反应进行基因层面的分析。未来,深入研究IL-17基因多态性与银屑病的关系对银屑病的治疗有重要临床意义。

细胞色素P450基因单核苷酸多态性与乙肝肝硬化易感性研究

目的初步探索细胞色素P 450基因SNP位点多态性是否与乙肝肝硬化的发生风险相关。方法本研究通过文献调研后从生物信息学数据库筛选细胞色素P 450基因上的10个位点,收集乙肝肝硬化组255例及健康组160例样本通过测序进行基因分型。应用Logistic回归等统计学分析验证基因SNP位点与乙肝肝硬化易感性。结果所有的SNP位点基因型分布均符合Hardy-Weinberg平衡。χ^(2)检验显示10个位点中仅rs3758581位点基因型及等位基因分布在乙肝肝硬化组与健康组间,差异有统计学意义。调整协变量的Logistic回归分析可见,rs3758581中共显性、加性、显性及超显性模型提示GA基因型患乙肝肝硬化风险升高。结论细胞色素P 450基因中rs3758581位点杂合突变GA基因型可能会增加乙肝肝硬化风险。

普乐可复血药浓度与肝药酶P450 3AP1和多药耐药基因多态性的关系

目的 :探讨普乐可复血药浓度的个体间差异与其在体内吸收、代谢相关基因肝药酶P4 5 0 3AP1(CYP3AP1)和多药耐药基因 1(MDR1)多态性的关系。 方法 :观察 4 1例口服普乐可复治疗的狼疮或膜性肾病患者的体重、普乐可复剂量、普乐可复全血谷浓度 ,并利用PCR 限制性片断长度多态性的方法检测患者CYP 3AP1基因— 4 4位A/G和MDR1基因 3435位C/T多态性 ,分析浓度 /剂量比与基因型的关系。 结果 :CYP 3AP1基因为AA型患者的血药浓度明显高于AG或GG型 (15 1 3± 93 4 ,n =2 1vs6 9 2± 39 4 ,n =2 0 ,P <0 0 0 1) ,MDR1基因为CC型患者的血药浓度明显低于CT或TT型 (73 7± 38 2 ,n =12vs 12 6 8± 91 3,n =2 9,P <0 0 5 )。 结论 :CYP 3AP1和MDR1基因多态性与普乐可复的血药浓度显著相关。根据上述基因不同基因型药物代谢的特点 ,有针对性地进行剂量调整 ,或在用药前通过检测基因型更合理地选择患者 ,有助于提高普乐可复的疗效 。

河北汉族人群白细胞介素-17血清表达水平及基因多态性与乙型肝炎病毒感染的关系

目的:探讨白细胞介素-17(IL-17)血清表达水平及基因IL-17-197A/G位点单核苷酸多态性与乙型肝炎病毒(HBV)感染及临床转归之间的关系。方法:以222例慢性HBV感染者作为病例组,以88例自限性HBV感染者为对照组。采用PCR结合荧光探针的体外DNA扩增检测技术,定量检测血清标本中的HBV DNA含量;ELISA试剂盒检测血清IL-17表达水平;采用贝克曼SNP分析仪,检测IL-17-197A/G位点基因型及等位基因分布频率。结果:各实验组IL-17表达水平差异具有统计学意义(F=158.1,r^2=0.61,P<0.000 1)。L-17-197A/G位点AA、AG和GG基因型分布频率在各组中的比较,差异具有统计学意义(χ~2=46.20,P<0.000 1)。GG基因型在自限性感染组中分布频率最高(78.41%),而在慢性乙肝肝硬化组中分布频率最低(19.05%)。AA基因型在慢性乙型肝炎肝硬化组中分布频率最高(67.72%)。结论:IL-17-197A/G位点AA基因型和A等位基因是河北汉族人群中HBV易感的宿主基因。

miR-17-92启动子区多态性在广西人群中分布及与淋巴细胞关系

目的:研究广西人群中miR-17-92基因簇启动子区rs9515692C/T和rs1352743A/G多态性分布特点和在不同人群间分布差异,探讨其多态性和淋巴细胞的关系。方法:采取多重单碱基延伸法(SNaPshot)和DNA测序法进行基因分型。运用流式细胞仪检测淋巴细胞数。数据分析利用SPSS17.0统计学软件。结果:2位点基因型及等位基因频率在广西人群的不同性别间差异无统计学意义(P>0.05)。rs9515692C/T和rs1352743A/G基因型及等位基因频率与国际人类基因组单体型图计划(HapMap)公布的欧洲、日本和非洲人群的比较差异有统计学意义(P<0.05)。结论:rs9515692C/T和rs1352743A/G基因多态性在不同人群中存在着不同程度差异。此外,rs9515692C/T多态性与B淋巴细胞数有关。