血清同型半胱氨酸及亚甲基四氢叶酸还原酶与先兆流产相关性研究

目的探讨血清同型半胱氨酸(Hcy)水平及亚甲基四氢叶酸还原酶基因(MTHFR)C677T、A1298C位点多态性与先兆流产的关系。方法以93例先兆流产患者为病例组,99例健康孕妇为对照组,采用荧光定量PCR技术检测MTHFR基因C677T和A1298C位点多态性,同时应用酶循环法测定血清Hcy水平。比较病例组和对照组间基因型分布频率和血清Hcy水平差异。结果病例组血清Hcy水平明显高于对照组;高Hcy是先兆流产的危险因素(OR=2.056,P=0.016);MTHFR C677TT基因型携带者血清Hcy水平明显高于其他基因型;A1298CC基因型携带者血清Hcy水平明显高于AA野合型;病例组A1298CC纯合基因频率明显高于对照组;差异均有统计学意义(P0.05)。结论 Hcy升高是导致先兆流产的重要危险因素;MTHFR A1298CC纯合突变可致血清Hcy水平升高与先兆流产的发生有一定的相关性。     

Red cell antioxidant enzymes and prognostic indexes in patients with burns

Red cell superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were measured in 66 burned patients (57 men, 9 women, age 16–78 years). BSAB varied from 15 to 93% and ABSI from 3 to 14 points. In the first week after injury the activity of SOD was significantly decreased as compared with the activity of the enzymes in the control group and was also below the reference values. Later the activity of SOD increased up to the normal range. The activity of CAT followed a similar pattern but the differences were not significant. No significant changes in red cell GPX were found during the monitored period. We did not find any significant association between the antioxidant enzyme activities and the markers of burns severity. On the other side there was a significant indirect association between the change of SOD activity (calculated as a difference between the first week values after the injury and the activities measured later) and BSAB.     

Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C?→?T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case–control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p?<?0.00001, Asians: p?=?0.0002, Caucasians: p?=?0.02, Africans: p?<?0.00001; TT genotype: Overall population: p?<?0.00001, Asians: p?=?0.0003, Caucasians: p?=?0.008, Africans: p?=?0.0003). Furthermore, the analysis suggested that the CC genotype might play a protective role against DN onset in patients with type 2 diabetes for the overall population, Asians, Caucasian and Africans. However, due to the limited sample size in the African population, these results should be interpreted with care. In conclusion, the MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies.     

MTHFR和MTRR基因多态性与急性脑梗死的关联分析

目的探讨亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与急性脑梗死(ACI)的关联。方法以130例ACI患者为病例组,130例体检健康者为健康对照组,PCR-荧光探针法对两组人群MTHFR基因677CT、1298AC位点和MTRR基因66AG位点的多态性进行定性检测,分析两组人群的基因型及其分布,酶法检测血清同型半胱氨酸(Hcy)水平。结果与健康对照组比较,ACI组MTHFR 677CT的T等位基因频率、MTRR 66AG的G等位基因频率显著升高(χ~2=21.03,P0.01和χ~2=12.45,P0.01),而MTHFR 1298AC差异无统计学意义(P0.05)。此外,与健康对照组比较,ACI组血清Hcy明显升高(P0.01),血清Hcy水平在MTHFR 677CT、MTHFR 1298AC及MTRR 66AG的基因型间差异具有统计学意义(P0.05)。结论 MTHFR 677 T等位基因、MTRR 66 G等位基因与ACI密切相关,MTHFR 1298AC未发现与ACI相关,3位点SNP均与ACI患者Hcy水平升高有关。     

Interaction between the MTHFR C677T polymorphism and traumatic childhood events predicts depression

Childhood trauma is associated with the onset and recurrence of major depressive disorder (MDD). The thermolabile T variant of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) is associated with a limited (oxidative) stress defense. Therefore, C677T MTHFR could be a potential predictor for depressive symptomatology and MDD recurrence in the context of traumatic stress during early life. We investigated the interaction between the C677T MTHFR variant and exposure to traumatic childhood events (TCEs) on MDD recurrence during a 5.5-year follow-up in a discovery sample of 124 patients with recurrent MDD and, in an independent replication sample, on depressive symptomatology in 665 healthy individuals from the general population. In the discovery sample, Cox regression analysis revealed a significant interaction between MTHFR genotype and TCEs on MDD recurrence (P=0.017). Over the 5.5-year follow-up period, median time to recurrence was 191 days for T-allele carrying patients who experienced TCEs (T+ and TCE+); 461 days for T− and TCE+ patients; 773 days for T+ and TCE− patients and 866 days for T− and TCE− patients. In the replication sample, a significant interaction was present between the MTHFR genotype and TCEs on depressive symptomatology (P=0.002). Our results show that the effects of TCEs on the prospectively assessed recurrence of MDD and self-reported depressive symptoms in the general population depend on the MTHFR genotype. In conclusion, T-allele carriers may be at an increased risk for depressive symptoms or MDD recurrence after exposure to childhood trauma.     

MTHFR基因多态性和同型半胱氨酸在冠心病脑梗死和糖尿病中的分析

目的探讨冠心病、脑梗死、糖尿病患者亚甲基四氢叶酸还原酶（MTHFR）和血浆同型半胱氨酸（Hcy）的关系,对三个病种的MTHFR基因型进行分析。方法收集120例冠心病,214例脑梗死,112例糖尿病患者及98例健康体检者标本,采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术检测MTHFRC677T基因,采用酶循环法检测血浆Hcy,比较四组MTHFRC677T基因多态性及血浆Hcy的差异。结果（1）MTHFR基因型在冠心病,脑梗死和糖尿病组与健康对照组间差异无统计学意义（P＝0．670）;（2）MTHFR基因频率在冠心病,脑梗死和糖尿病组与健康对照组间差异无统计学意义（P＝0．721）;（3）冠心病组和脑梗死组的MTHFR基因TT型患者的Hcy水平远远高于CC型和CT型患者（F＝6．212,P＝0．003;F＝44． 362,P＝0．000）。结论不同病种间MTHFR基因型和基因频率差异无统计学意义,但冠心病组和脑梗死组MTHFR基因TT型患者Hcy水平则远远高于CC型和CT型患者,差异有统计学意义。     

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student’s t test.Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 μmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 μmol/L, t=1.08, P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.