Lack of association between TNFα rs1800629 polymorphism and schizophrenia risk: A meta-analysis

Evidence has suggested that tumour necrosis factor α (TNFα) may be involved in the aetiology of schizophrenia, but the underlying association between TNFα-308G/A polymorphism (rs1800629) and schizophrenia risk is still ambiguous. This meta-analysis was performed to quantitatively summarise the evidence for such a relationship. Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedical Literature Database) and WANFANG databases within a range of published years from 1990 to July 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI) was used to assess the different associations. Twenty-one studies with 4340 cases and 5745 controls were included in this meta-analysis. The pooled examination displayed that there was no significant association between TNFα-308G/A polymorphism and susceptibility to schizophrenia overall (OR=1.047, 95% CI=0.876–1.253, P=0.614 for A vs. G), and no difference in Caucasian subgroup (OR=1.041, 95% CI=0.815–1.331, P=0.747) and Asian subgroup (OR=1.057, 95% CI=0.807–1.386, P=0.686). Lack of association was also found in males (OR=0.862, 95% CI=0.413–1.797, P=0.692) and females (OR=0.797, 95% CI=0.579–1.097, P=0.163) with a dominant model. Taken together, this meta-analysis suggests that TNFα-308G/A polymorphism may not be associated with schizophrenia susceptibility.     

Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene polymorphisms and associated risk of cardiovascular diseases: A study from Jammu region

AimPotent risk factors at both genetic and non-genetic levels are accountable for susceptibility and instigation of different cardiovascular phenotypes. Recently, homocysteine is being identified as an important predictor for cardiovascular diseases. Homocysteine remethylation plays a key role in the synthesis of methionine and S-adenosine methionine. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes are known to regulate the homocysteine remethylation reaction and higher homocysteine level is significantly associated with diverse cardiovascular phenotypes. In this context, we aimed to carry out a study on the association of MTHFR (C677T) and MTR (A2756G) gene polymorphism with CVD in population of Jammu region of J&K state.Materials and methodsA total of 435 individuals were enrolled (195 CVD patients and 240 controls) for the case–control study. Genotyping of MTHFR C677T and MTR A2756G gene polymorphism was done by PCR-RFLP technique. Biochemical parameters were estimated by biochemical analyser.ResultsMetabolic variables such as serum LDL-C, TC and TG were significantly higher in patients (p < 0.0001), whereas serum HDL-C was higher in controls. Majority of the patients were having history of hypertension (57.44%; p < 0.0001) as a concomitant condition. The evaluation of genetic association showed that, MTHFR C6877T (OR: 8.89, 95% CI: 2.01–39.40) and MTR A2756G (OR: 1.48, 95% CI: 1.09–2.00) polymorphisms associated with higher risk of CVD.ConclusionThe present study reveals significant differences in nongenetic variables among patients and control as well as association of gene polymorphisms with CVD risk.     

DNA修复基因hOGG1的寡核苷酸多态性与癌症遗传易感性的关系

该文从基因结构、生物学功能和基因寡核苷酸多态性与疾病发生等方面探讨人源8-羟基鸟嘌呤DNA糖苷酶(hOGG1)基因在DNA损伤修复中的作用及其基因寡核苷酸多态性与癌症的遗传易感性的关系；综述hOGG1基因与癌症遗传易感性的分子流行病学研究；探讨hOGG1基因寡核苷酸多态性与辐射致癌的关系；指出hOGG1基因作为癌症易感人群诊断和预防标志物的价值.     

Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations

BACKGROUND: Cytosolic aldehyde dehydrogenase, or ALDH1A1, functions in ethanol detoxification, metabolism of neurotransmitters, and synthesis of retinoic acid. Because the promoter region of a gene can influence gene expression, the ALDH1A1 promoter regions were studied to identify polymorphism, to assess their functional significance, and to determine whether they were associated with a risk for developing alcoholism. METHODS: Sequence analysis was performed in the promoter region by using Asian, Caucasian, and African American subjects. The resulting polymorphisms were assessed for frequency in Asian, Caucasian, Jewish, and African American populations and tested for associations with alcohol dependence in Asian and African American populations of alcoholics and controls. The functional significance of each polymorphism was determined through in vitro expression analysis by using HeLa and HepG2 cells. RESULTS: Two polymorphisms, a 17 base pair (bp) deletion (-416/-432) and a 3 bp insertion (-524), were discovered in the ALDH1A1 promoter region: ALDH1A1*2 and ALDH1A1*3, respectively. ALDH1A1*2 was observed at frequencies of 0.035, 0.023, 0.023, and 0.012 in the Asian, Caucasian, Jewish, and African American populations, respectively. ALDH1A1*3 was observed only in the African American population, at a frequency of 0.029. By using HeLa and HepG2 cells for in vitro expression, the activity of the luciferase reporter gene was significantly decreased after transient transfection of ALDH1A1*3-luciferase compared with the wild-type construct ALDH1A1*1-luciferase. In an African American population, a trend for higher frequencies of the ALDH1A1*2 and ALDH1A1*3 alleles was observed in a population of alcoholics (p = 0.03 and f = 0.12, respectively) compared with the control population. CONCLUSIONS: ALDH1A1*2 and ALDH1A1*3 may influence ALDH1A1 gene expression. Both ALDH1A1*2 and ALDH1A1*3 produce a trend in an African American population that may be indicative of an association with alcoholism; however, more samples are required to validate this observation. The underlying mechanisms contributing to these trends are still unknown.     

上海大学生非酒精性脂肪肝与载脂蛋白E基因多态性的关系

目的 探讨上海大学生非酒精性脂肪肝(NAFLD)的患病率及与载脂蛋白E(ApoE)基因多态性的相关性.方法 对上海同济大学4 148名在校学生进行问卷调查;采用肝脏超声以及血肝功能、脂蛋白等生化指标检测,将确诊的NAFLD患者与正常者200例,进行外周血PCR-RFLP检测ApoE基因多态性.结果 (1)4 148名大学生中NAFLD检出398例(9.6%),NAFLD患者的体重指数、腰臀比、甘油三酯、总胆固醇、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰转移酶均高于对照组(P＜0.01),且随NAFLD程度加重,有递增趋势.(2)NAFLD组和对照组ApoE基因型分布比较差异显著(,P＜0.01).NAFLD E4/4基因型分布频率(5.5%)明显升高,E3/3分布频率(61.8%)明显减低(均P＜0.01).(3)非条件logistic回归分析显示总胆固醇、低密度脂蛋白胆固醇、腰臀比、AST、ALT、GGT与E4/4基因型密切相关.结论 ApoE基因112位和158位的氨基酸残基发生相应的变化可引起不同程度的脂质代谢障碍,E4/4可能是导致NAFLD发生的遗传因素之一.     

<Emphasis Type="Italic">GSTP1</Emphasis> and <Emphasis Type="Italic">MDR1</Emphasis> Genotypes and Central Nervous System Relapse in Childhood Acute Lymphoblastic Leukemia

The probability of event-free survival of childhood acute lymphoblastic leukemia (ALL) approaches 80% or more with the use of modern multiagent chemotherapeutic regimens. One major contribution to this success has been reduction of the rate of central nervous system (CNS) relapses to less than 5%. However, heterogeneity is observed with regard to the incidence of CNS relapse in homogenously treated patient populations. One potential explanation for this heterogeneity is variation in the genetic background of these populations. Glutathione S-transferase P1 and P-glycoprotein are implicated in resistance to a variety of chemotherapeutic agents and have been localized to the blood-brain barrier. In a matched case-control study, we investigated the associations between CNS relapse in childhood ALL and the presence of phenotypically relevant single nucleotide polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding for Pgp; exon 26, C3435T). Significant reductions in risk of CNS relapse were observed for patients homozygous for the GSTP1 Val105 allele as well as for patients with the MDR1 3435T/T or C/T genotype. For both genotypes, the effect was restricted to patients at intermediate or high risk of treatment failure. These results suggested a modulating role for host genetic variation in the development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt-Münster protocols.     

Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis

Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractantprotein-1 (MCP-1; A-2518G), stromal cell-derived factor-1ß(SDF-1ß; G801A), and C–C chemokine receptor-5(CCR5; 32) genes have been associated with functional effects.These chemokines have been implicated in leucocyte recruitmentto arterial lesions. In a case-control study, we explored relationsbetween these polymorphisms and coronary artery disease (CAD),with respect to angiographic abnormalities and acute coronarysyndromes (ACS). Methods and Results The LUdwigshafen Risk and Cardiovascularhealth (LURIC) cohort was genotyped by RFLP-PCR. Based on coronaryangiography, individuals were sub-divided into CAD cases and controls . RANTES-403 genotype frequencies were significantly different in cases and controls, as were A allele carrier frequencies (36.01% vs. 30.19%, OR=1.30 [95%-CI=1.06–1.60], ). By multivariate analysis, RANTES A-403 retained significantassociation with CAD . RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.08–1.71],). MCP-1 G-2518, SDF-1ß A801, and CCR5 32 were not associated with CAD. Conclusions RANTES A-403 was associated with CAD independentlyfrom conventional risk factors and CRP or fibrinogen as inflammatorybiomarkers. The association was enhanced in smokers and ACS,conditions where platelet activation and inflammation predominate.RANTES A-403 may increase genetic susceptibility to CAD.     

同型半胱氨酸及其相关酶基因多态性与糖尿病周围神经病变的关系

研究对象为 2型糖尿病 (DM )有周围神经病变组 (60例 )、2型DM无周围神经病变组 (4 6例 )和正常对照组 (5 0例 )。分别测定 3组血浆同型半胱氨酸 (Hcy) ,血清叶酸、维生素B12 水平及Hcy代谢关键酶亚甲基四氢叶酸还原酶 (MTHFR)的基因型。结果显示 ,高Hcy及低叶酸、维生素B12 水平与 2型DM患者伴发周围神经病变相关 ,而MTHFR的基因多态性只与DM有关而与DM周围神经病变无相关性。