蛋白激酶B1基因多态性与重性抑郁障碍事件相关电位的关联性研究

Objective To explore the relationship of protein kinase B1 ( PKB1 ) gene polymorphisms in PI3-K pathway of BDNF and event-related potentials in depression.Methods The design of case-control research was used ,and 91 major depressive patients and 65 normal controls who were made in age and gender matched with patients were measured auditory event-related potential P300 and contingent negative variation ( CNV ) in the day when two groups were collected.Polymerase chain reaction (PCR) and direct DNA sequencing technology were used to detect PKB1 gene polymorphisms.Three SNPs that named rs3001371 ,rs2494738 ,rs1130214 were selected from 3 representative BLOCK Districts of PKB1.Two independent samples t test was used to analysis P300 and CNV between two groups,and the same way to analysis the average level of P300 and CNV and PKB1 SNP genolatency of P2(P＜0.05) and lower amplitude of P3a(P＜0.01 ) ,P3b(P＜0.01 ) and P3 (P＜0.01 ) ;CNV had der had statistical difference (P＜ 0.05 )in PKB1 rs3001371 gene between C/C and C/T genotype combined which included C allele, and T/T genotype.The amplitude of P3a( (5.93 ± 2.35 ) μV, P3b(6.51 ± 3.00) μV, P3 (6.27±2.43) μV) were lower than TT Genotype ( (7.45 ±2.19)μV, (8.63 ±3.57)μV,(8.04 ±2.57)μV,respectively).The mean of CNV indicators were not found different in statistics among the rs3001371 genotypes.Conclusions PKB1 gene rs3001371 polymorphism is associated with the principal component of P300 amplitude in patients with Major depressive disorder which suggest that genetic factors may have a certain impact on cognitive function in the patients with Major depressive disorder.     

蛋白激酶B1基因多态性与重性抑郁障碍事件相关电位的关联性研究

Objective To explore the relationship of protein kinase B1 ( PKB1 ) gene polymorphisms in PI3-K pathway of BDNF and event-related potentials in depression.Methods The design of case-control research was used ,and 91 major depressive patients and 65 normal controls who were made in age and gender matched with patients were measured auditory event-related potential P300 and contingent negative variation ( CNV ) in the day when two groups were collected.Polymerase chain reaction (PCR) and direct DNA sequencing technology were used to detect PKB1 gene polymorphisms.Three SNPs that named rs3001371 ,rs2494738 ,rs1130214 were selected from 3 representative BLOCK Districts of PKB1.Two independent samples t test was used to analysis P300 and CNV between two groups,and the same way to analysis the average level of P300 and CNV and PKB1 SNP genolatency of P2(P＜0.05) and lower amplitude of P3a(P＜0.01 ) ,P3b(P＜0.01 ) and P3 (P＜0.01 ) ;CNV had der had statistical difference (P＜ 0.05 )in PKB1 rs3001371 gene between C/C and C/T genotype combined which included C allele, and T/T genotype.The amplitude of P3a( (5.93 ± 2.35 ) μV, P3b(6.51 ± 3.00) μV, P3 (6.27±2.43) μV) were lower than TT Genotype ( (7.45 ±2.19)μV, (8.63 ±3.57)μV,(8.04 ±2.57)μV,respectively).The mean of CNV indicators were not found different in statistics among the rs3001371 genotypes.Conclusions PKB1 gene rs3001371 polymorphism is associated with the principal component of P300 amplitude in patients with Major depressive disorder which suggest that genetic factors may have a certain impact on cognitive function in the patients with Major depressive disorder.     

Relationship between matrix metalloproteinase-9 polymorphism and acute coronary syndrome

Objective： To investigate the relationship of matrix metalloproteinase-9 polymorphism to acute coronary syndrome and its affect on the severity of coronary artery disease. Methods： By means of polymerase chain reaction （PCR） and restriction fragment length polymorphism, genotypes of 245 patients with acute coronary syndrome（ACS） and 205 healthy subjects were tested. Genotypes displaying C-1562T functional promoter polymorphism （of the MMP-9 gene） were determined. The relationship between the polymorphism of the MMP-9 gene and ACS and the severity of coronary vessels diseased was analyzed. Results： The frequency of C/T plus T/T genotypes and T allele in patients with ACS was significantly higher than that in healthy subjects （22.1% vs 12.7% and 11.4% vs 6.6% respectively）. But they were not associated with the number of coronary arteries diseased. Conclusion： The MMP-9 polymorphism may be susceptible to ACS. But there was not significant difference between the AMI and UAP subgroups.     

Osteopontin gene polymorphism in association with systemic lupus erythematosus in Chinese patients

Background Osteopontin (OPN) is one kind of cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Some researches have showed that OPN may be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate possible association of a single nucleotide polymorphism（SNP）at position 9250 in exon 7 of the OPN gene (OPN gene 9250) with SLE in Chinese patients.Methods Totally 158 patients (18 males and 140 females) fulfilled the revised criteria for SLE by the American College of Rheumatology in 1982 and 180 healthy volunteer controls (34 males and 146 females), all from the south of China, consented to participate in the study. OPN gene 9250 polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results The frequency of TT genotype of the OPN gene 9250 was significantly lower (52.5% vs 70%, P<0.05) and the frequency of TC genotype of the OPN gene 9250 was significantly higher (43.7% vs 29.4%, P<0.05) in SLE patients than in controls. There were significant differences in OPN gene 9250 allele and phenotype frequencies between the SLE patients and controls (P<0.05). When the SLE patients and controls were separated into men and women, significant differences of frequencies were noted in TT genotype, TC genotype and allele of the OPN gene 9250 in women (P<0.05) but not in men (P>0.05). Conclusions OPN gene 9250 polymorphism appears to be associated with susceptibility to SLE in Chinese Han ethnic population.     

C509T and T869C polymorphisms of transforming growth factor β1 and the risk of IgA nephropathy: a meta-analysis

Background IgA nephropathy （IgAN） is the most common primary glomerular disease.Transforming growth factor β1 （TGFβ1） plays an important role in pathogenesis of IgAN.Associations between the polymorphisms of TGFβ1 gene and the risk of IgAN remained inconsistent.A meta-analysis was conducted to investigate the association between polymorphisms in the TGFβ1 gene and IgAN susceptibility.Methods Databases including Pubmed,EMBASE,ISI,et al.were searched to find relevant studies.Odds ratios （ORs）with 95％ confidence intervals （CIs） were used to evaluate the strength of associations.Results Ten studies involving 1770 cases and 1953 controls were included.Significant association between C509T polymorphism and IgAN risk was observed （OR 1.42,95％ CI 1.12-1.81,P=0.0004; I2=0％） in Caucasians by the overdominant model （CT vs.CC ＋ TT）,but no significant association was found （P=0.200） in Asians by the dominant model （CC ＋ CT vs.TT）.Significant association between T869C polymorphism and IgAN susceptibility was found （OR 1.21,95％ CI 1.02-1.44,P=0.030） in overall populations by the dominant model （TT ＋ TC vs.CC）.Subgroup analysis found T allele of T869C polymorphism was associated with IgAN susceptibility in Caucasians （P=0.030）,but not in Asians （P=0.290）.Conclusion Both heterozygotes of C509T polymorphism and T allele of T869C polymorphism in TGFβ1 were associated with the risk of IgAN in Caucasians,but not in Asians.     

DISTRIBUTION OF AN NcoI POLYMORPHISM IN THE LYMPHOTOXIN α GENE IN DUTCH PATIENTS WITH INFLAMATORY BOWEL DISEASES

An Ncol restriction fragment length polymorphism in the first intron of the lymphotoxin α gene was investigated in 35 patients with Crohn's disease, 40 patients with ulcerative colitis, and 30 unrelated healthy controls, all of Dutch origin. The results showed that no significant differences existed in the genotype frequencies of the NcoI polymorphism in the first intron of the LTα gene between ulcerative colitis patients or Crohn's disease patients and the healthy controls. The study indicates that the NcoI polymorphism in the LTα gene can not be used as a genetic marker for the predisposition to inflammatory bowel diseases. However, since this polymorphism may control the production of tumor necrosis factor, study of this and other related tumor necrosis factor gene polymorphisms may he used as markers to identify patient subgroups and to define patient heterogeneity. Further studies are being carried out on other polymorphisms and on the relevance of LTα and TNFα haplotypes.     

The Relationship of Insulin—receptor Gene Polymorphism to Ischemic Stroke？

Objective To investigate the role of mutation of insulin-receptor(INSR) gene in the development of ischemic stroke.Methods The base-variations at exon 17 and 20 of INSR gene,by means of PCR-SSCP were determined in 68 cases of atherothrombotic cerebral infarction (ACI),81 cases of lacunar infarction(LI) and 62 healthy controls(HC).Results There were 2 alleles of T and C at exon 17 of INSR gene.The prevalence of mutant of t allele in ACI patients was more common than that in the controls.the blood pressure and the parameters of lipid metabolism in the patients with mutant were higher than those in the controls with wild-type gene.However,the correlative analysis showed that the polymorphism of INSR gene was not related statistically to the blood pressure.No base-variation at exon 20 was found in the study.Conclusion The mutation at exon 17 of INSR gene,by promoting the development of atherosclerosis,may participate in the occurrence of ischemic stroke.     

Atrial natriuretic peptide gene polymorphism is not associated with hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy （HCM） is a primary autosomal dominant inheritant myocardial disease with heterogeneity in clinical manifestations, natural history and prognosis. Even carrying an identical gene mutation among family members, a va[iety of clinical phenotypes have been found in patients with HCM. Modifier genes may contribute to the diversity. The plasma levels of atrial natriuretic peptides （ANP） were found previously to be elevated in HCM. Our studies suggested that ANP gene promoter polymorphism is associated with left ventricular hypertrophy in hypertension. The present study aimed to determine whether the two SNPs in the ANP gene are associated with HCM Methods We determined the relationships between the ANP gene polymorphism and HCM in 262 HCM patients and 614 age- and sex-matched healthy individuals. All of the subjects were genotyped for -A2843G and A188G polymorphisms. Results The genotype frequency in the -A2843G and A188G polymorphisms of the ANP gene was not significantly different between the HCM patients and controls. The -A2843G and A188G polymorphisms were also not associated with clinical phenotype in cardiomyopathy patients. Conclusions The polymorphisms of the ANP gene are not associated with increasing risk of HCM or clinical phenotypes. The variations of the ANP gene may not serve as a genetic modifier for the development of HCM.     

A meta-analysis of relationship between β-fibrinogen gene -148C/T polymorphism and susceptibility to cerebral infarction in Han Chinese

Objective The results of studies on association between -148C/T polymorphism in promoter region of β-fibrinogen gene and susceptibility to cerebral infarction in Chinese population are controversial. In this study, we summarize the results of published works in this field by a meta-analysis. Data sources Genetic association studies evaluating the β-fibrinogen gene -148C/T polymorphisms and cerebral infarction involving Chinese population published before December 2005 were collected from PubMed, EMBASE and CNKI. Study selection Case control studies involving unrelated, Han subjects aged from 18 to 80 years, and the internationally recognized diagnostic standard of cerebral infarction and genotype frequencies in control group consistent with Hardy-Weinberg equilibrium were used. Publication bias was tested by funnel plot and the odds ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies. The software Review Manager (Version 4.2) was used for meta-analysis. Results Eleven studies including 1223 patients and 1433 controls met the selection criteria. There was no heterogeneity among the odds ratios (ORs) of individual studies (χ(2)=17.82, P=0.06). The combined OR of susceptibility to cerebral infarction in -148T allele carriers compared to the wild homozygote was 1.32 (95%CI 1.12 to 1.55, P=0.0008). In the patients with cerebral infarction, the average plasma fibrinogen level of allele T carrier was 0.42 g/L (95%CI 0.29 to 0.54, P<0.001), higher than that of -148C/C homozygous ones. Conclusions β-fibrinogen gene -148C/T polymorphism might contribute to susceptibility to cerebral infarction in Han Chinese. To reach a definitive conclusion, further gene to gene and gene to environment interactions studies on β-fibrinogen polymorphisms and cerebral infarction with large sample size are required.