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Aims: The assessment of polymorphisms CYP2C9*2 (430С>Т; rs1799853) and CYP2E1*1B (–C9896G, rs2070676) role of the genes of cytochrome Р450 in pathogenesis of the chronic viral hepatitis C (HCV) in Uzbek population became the main aim. Place and Duration of Study: The molecular and genetic study of biomaterial was accomplished under Department of Molecular Medicine and Cellular Technologies of SRIH&BT (Scientific Research Institute of Hematology and Blood Transfusion), MoH RUz in the period of 2013-2016. Methodology and Study Design: Genotyping assay of polymorphism of the genes under study was accomplished by the standard polymerase chain reaction (PCR). Peripheral blood of 107 patients with diagnosis chronic viral hepatitis C included in the main group and 81 relatively healthy donors (test group) was used for the molecular and genetic study of CYP2Е1*1В and CYP2C9*2 polymorphisms. Results: Comparative analysis revealed differences in the distribution of allele frequencies of polymorphisms 430C > T CYP2C9 gene and gene C9896G CYP2E1 * 1B in groups of patients with chronic HCV group and population control. In the main group of patients with chronic HCV mutant allele "T » CYP2C9 gene met significantly more frequently in comparison with the control group population. Thus, the highest frequency of the mutant allele of the "T", as compared with the control group was observed in patients with moderate HCV activity. This is the lowest frequency of this genotype was observed in the subgroup of patients with liver cirrhosis. Our studies have shown that the accumulation of the mutant allele «G» CYP2E1 * 1B gene was also the case in almost all sub-groups of patients with chronic HCV. The frequency of heterozygous genotype CYP2E1*1B polymorphism in the population control group was 13.6%. It should be noted that the highest frequency component of genotype C/G was detected in the group of patients with chronic HCV with high activity. The data obtained indicate an association genotype C/G with the activation process of inflammation and fibrotic changes. Conclusion: The results showed a high frequency of mutant allele "T" polymorphism 430C > T CYP2C9 with HCV, which allows us to consider the CYP2C9 gene as a factor of a favorable outcome of chronic hepatitis C. The association between the expression of CYP2E1 * 1B and progression of the disease with activation fibrosis-formation in individuals of Uzbek population is an important factor in the development of personalized therapy.
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Objective To investigate the association of neural differentiation factor 1 (NeuroD1) Ala45Thr polymorphism with type 2 diabetes by meta-analysis.Methods The electronic databases were retrieved from PubMed,EMBASE,CNKI,VIP fulltext database,and Wanfang fulltext database.Literatures about the association of NeuroD1 Ala45Thr polymorphism with type 2 diabetes from 2004 to 2012 were searched.The selected studies from 2004 to 2012 were included to analyze data based on the published meta-analysis of the NeuroD1 (Ala45Thr) gene polymorphism and type 2 diabetes written by Kavvoura,et al.The odds ratio of NeuroD1 (Ala45Thr) genotype distributions in type 2 diabetic patients compared with healthy control were analyzed.Rev-Man 5.0 software was applied for investigating hereogeneity among individual studies and summarizing effects with proper statistical methods.Thirteen case control studies were enrolled.Results A total of 3 896 patients and 3 186 control subjects were enrolled for the study.The pooled ORs of Thr45Thr45/(Ala45Thr+ Ala45Ala45) genotype in type 2 diabetes mellitus and control groups were 3.16 (95％ CI0.99-10.11) in the subgroup of yellow race and 1.09(95％ CI0.90-1.32) in the subgroup of white race,with no statistically significant difference(P＞0.05).The pooled OR of G/A allele in type 2 diabetes mellitus and control groups was 0.85 (95 ％ CI 0.72-0.99)/1.18 (95％ CI 1.07-1.38),with statistically significant difference (Z =2.02,P =0.04).Conclusions The A allele of NeuroD1 (Ala45Thr) locus may be a risk factor for type 2 diabetes mellitus.
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Objective To investigate the relationship between APE1, XRCC1 gene polymorphisms and hepatocellular carcinoma(HCC) susceptibility and to explore the correlation of APE1, XRCC1 gene polymorphisms with the sensitivity to platinum-based drugs .Methods Seventy-eight HCC patients and 80 controls were selected .By PCR and RFLP , the single nucleotide polymorphism of APE1 Asp148Glu and XRCC1 Arg194Trp genes and the susceptibility of HCC or platinum drug sensitivity were analyzed.Results The Glu/Glu genotype of APE1 could increase in the risk of HCC by 7.21 times (95%CI:1.325-29.109) (P<0.05).APE1 and XRCC1 gene polymorphisms could also affect the platinum drug resistance of HCC patients.Conclusion APE1 Asp148Glu is correlated with the susceptibility to HCC .APE1 and XRCC1 genes can be considered a target for therapy to improve the sensitivity of HCC platinum drugs .
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The association of interleukin 6 receptor ( IL-6R ) gene - 183 A/G ( rs4845617 ) and Asp358 Ala (rs8192284 A/C) polymorphisms with metabolic syndrome was investigated in Chinese Han population.The result showed that the frequencies of AA genotype and A allele were higher in patients with metabolic syndrome ( MS ) than those in healthy subjects ( P＜0.05 or P＜0.01 ).The risk of MS in patients with A allele was 1.643 folds of that with allele C(95％ CI 1.163-2.320,P＜0.01 ).No differences were found in the genotype and allele frequencies of -183A/G between two groups ( P＞0.05 ).The Asp358Ala polymorphism of IL-6R was significantly associated with MS in Chinese Han population.
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Objective To investigate the association of uncoupling protein 2 ( UCP-2 ) gene promoter -866G＞A polymorphism and ischemic stroke in diabetic patients.Methods A total of 844 type 2 diabetic patients including 404 cases with ischemic stroke and 440 cases without ischemic stroke were selected for the 4 year prospective study,Genomic DNA was extracted from the whole blood samples of subjects,UCP-2 gene promoter -866G ＞ A polymorphism was detected by TaqMan MGB probe method,and then the genotype and allele gene frequencies were compared.Results The risk of ischemic stroke in type 2 diabetic female patients with AA+GA genotypes of UCP-2 was higher than that with GG genotype (P＜0.05),but there was no difference among male patients with three genotypes.Conclusions UCP-2 gene promoter -866G ＞ A polymorphism increases the risk of ischemic stroke in Chinese diabetic women.
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The polymorphisms of paraoxonase 1 ( PON 1 ) and ApoE gene in 192 patients with type 2diabetes mellitus (DM group) , 116 cases of atherosclerosis (AS) without DM (AS group), and 105 normal subjects (NC group ) were detected by means of PCR-restriction fragment length polymorphism. The serum concentration of Ox-LDL was determined by enzyme linked immunosorbent assay. The results showed that plasma Ox-LDL level in DM group was higher than those in AS and NC groups[(754.2±279.9 vs 526. 1±186.2 and 421.1 ± 163.2 )μg/L, P<0.01]. Ox-LDL level in the patients with QQ genotype of PON 1 was higher than those in QR and RR genotypes in type 2 DM[(846.6±147.5 vs 763.4±126. 7 and 7 1 3.2 ±132.4 ) μg/L, P<0. 0l],and Ox-LDL level in the patients with ε3/4+ ε4/4 genotype of ApoE was also higher than those in ε3/3 and ε2/2 + ε2/3 geneotypes in type 2 DM[( 824.3 ± 173.5 vs 741.6± 182. 5 and 718.3 ± 167.5 ) μg/L, P<0.05], but the difference was not found in atherosclerosis without DM. Multiple regression analysis showed that disease duration, PON1 and ApoE genotypes were the independent predictors of plasma Ox-LDL level in patients with type 2 DM.
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Objective To investigate the whole genomic expression profiles of chronic atrophic gastritis with interleukin(IL)-1β-31CC/-511TT genotype as measured by oligonucleotide microarray technique.Methods Genomic RNA was extracted from gastric biopsies of 12 patients with chronic atrophic gastritis(6 with IL-1β-31CC/-511TT and 6 with IL-1β-31TT/-511CC).The genomic profiles of IL-1β gene polymorphisms 31CC/-511TT and 31TT/-511CC were compared and tested for differential expressed genes associated with 31CC/-511TT using Agilent human whole genomic oligonucleotide microarrays.The results were further analyzed in terms of gene ontology(GO).Results There were 200 differentially expressed genes associated with IL-1β-31CC/-511TT,159 of which were up-regulated and 41 were down-regulated.These genes mainly involved in macromolecule metabolic process,post-translational protein modification,ubiquitin cycle,and protein kinase cascade.Five genes had biological activities,one of which was down-regulated gene(PCSK5)and 4 were upregulated genes(PRKCA,NPLOC4,TRIB3 and MAPKAPK3).Conclusions The chronic atrophic gastritis with IL-1β-31CC/-511TT genotype has molecular phenotypes which is associated with malignance and inflammation.These individuals are needed more intensive preemptive treatment and dynamic surveillance.
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@#ObjectiveTo investigate the relationship of the polymorphism of endothelial nitric oxide synthase (eNOS), the 27-bp variable number of tandem repeats (VNTR) in intron 4 with essential hypertension (EH) of the northern Han nationality in China.MethodsGenotypes, the level of plasma nitric oxide metabolites (NOx) and the activity of nitric oxide synthase (NOS) of 207 EH subjects and 231 healthy subjects were measured by polymerase chain-reaction (PCR).ResultsThe frequencies of ecNOS4a/a,ecNOS4b/a, and ecNOS4 b/b in the healthy group were 0.43%, 13.42% and 86.15% respectively. The frequency of the b allele was 92.86%, and the frequency of the a allele was 7.14%. While the frequencies of ecNOS4 a/a, ecNOS4 a/b,and ecNOS4 b/b in the EH group were 0.49%, 19.32% and 80.19% respectively. The frequency of the a allele in EH group (n=42, 10.15%) was significantly higher than that in the healthy group (n=33, 7.14%)(P<0.05). The plasma NOx level of the EH group was 70.04±14.68 mol/L, and significantly lower than that 84.09±27.27 mol/L in the healthy group (P<0.05). Similarly, both the plasma TNOS and iNOS activities of the EH group were 35.49±12.8 U/ml and 14.92±7.93 U/ml, and markedly lower than that 41.47±13.2 U/ml and 10.11±6.21U/ml in the healthy group (P<0.05). But the activities of eNOS in the EH group and healthy group were not significantly different (P>0.05).ConclusionThe variations of ecNOS4 gene locus may be responsible for the decrement of plasma NOx, both plasma NOx level and activity of NOS decreases in EH patients, so it may be a genetic susceptibility marker for EH of the Han nationality in China.
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The distributin of C81 of phenotypes in 203 Chinese Han populations in Liaoning area were studied using the ultra—thin polyacrylamide gel isoelectric focusing (PAGIEF) follwed by immunoblotting technique. The gene frequencies were as follows; C81 0.5567, C81 0.4433, The observed numbers of the phenotypes were in agreement with the expected numbers under the Hardy-Weinberg equilibrium. The gene frequencies among Chinese and other populations were compared.