Are common mutations of cystathionine β-synthase involved in the aetiology of neural tube defects?

Mildly elevated maternal plasma homocysteine (Hcy) levels (hyperhomocysteinemia) have recently been observed in some neural tube defect (NTD) pregnancies. Plasma levels of Hcy are governed by both genetic and nutritional factors and the aetiology of NTDs is also known to have both genetic and nutritional components. We therefore examined the frequency of relatively common mutations in the enzyme cystathionine β-synthase (CBS), which is one of the main enzymes that controls Hcy levels, in the NTD population. Neither the severely dysfunctional G307S CBS allele nor the recently reported 68 bp insertion/I278T CBS allele was observed at increased frequency in the cases relative to controls. We therefore conclude that loss of function CBS alleles do not account for a significant proportion of NTDs in Ireland.     

Why homocysteine is a risk factor of neurodegenerative diseases mini review

The receptor-mediated effects of homocysteine and homocysteic acid on neurons and lymphocytes are described. Activation of glutamate receptors by these ligands was shown to induce an increase in intracellular calcium concentration and the level of active forms of oxygen in both types of cells. This increase may serve as a signal for activation of apoptosis. Metabotropic receptors of group III stimulated the excitotoxic effect of homocysteine and homocysteic acid, while those of group I and II prevented it. It is proposed that selective agonists/antagonists of these metabotropic receptors can be used for correction of neuronal and immune cell metabolism during hyperhomocysteinemia.     

高同型半胱氨酸血症与复发性脑梗死

目的 :探讨高同型半胱氨酸血症(HHcy)与复发性脑梗死 (RCI)的关系 ,为缺血性脑血管病的二级预防开辟新的预防和治疗途径。方法:将80例急性脑梗死患者 ,分为首发性脑梗死组 (FCI组 )43例 ,复发性脑梗死组(RCI组 )37例 ,利用高效液相色谱法测定空腹血浆同型半胱氨酸(tHcy)水平 ,并与40例健康者(对照组)对照研究。结果 :⑴空腹血浆tHcy 水平RCI组为 (23.96±6.07) μmol/L ,FCI组为 (21.61±4.72) μmol/L ,两组比较差别有统计学意义 (P<0.05)。⑵FCI组中HHcy14例 ,发生率32.56 % ;RCI组中HHcy17例 ,发生率45.95% ,正常对照组HHcy40例 ,发生率5 %。RCI组HHcy 的检出率显著高于FCI组 ,且2者检出率均显著高于对照组(均P<0.05)。⑶空腹血浆tHcy水平与RCI具有显著相关性 ,而与高血压病、血脂异常、糖尿病、吸烟及饮酒等RCI可能的危险因素无显著相关性 ,提示HHcy 可能是RCI的一个独立的危险因素。结论 :HHcy与RCI关系密切 ,可能为其一个独立的危险因素。     

高同型半胱氨酸血症及MTHFR基因与中青年脑梗死的研究

目的 :探讨高同型半胱氨酸血症 (HHC)及N5,N10-亚甲四氢叶酸还原酶(MTHFR)基因型与中青年脑梗死的关系。方法 :采用高压液相色谱法及PCR -RFLP技术测定80例脑梗死患者和40例正常对照者的血浆总同型半胱氨酸水平 (tHcy)和MTHFR基因多态性。结果 :患者组中MTHFR基因T/T纯合型频率为33.75 % ,T等位基因频率为58.75 % ,显著高于对照组的20 %和36.25 % (P<0.05) ;患者组血浆tHcy均值为22.70μmol/L ,对照组仅为13.19μmol/L ,患者组HHC31例 ,对照组仅为2例 ,2组差别有统计学意义,且2组T/T型者血浆tHcy水平高于T/C型和C/C型者。结论 :MTHFR基因突变可能是脑梗死发生的一个遗传易感因素 ,tHcy可能与血脂血糖一样是脑卒中发病的一个独立危险因素     

Prevalence of Hyperhomocysteinemia in China: A Systematic Review and Meta-Analysis

Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 μmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3–97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.     

高同型半胱氨酸血症与心绞痛心肌缺血总负荷的关系

目的：研究高同型半胱氨酸水平与心绞痛心肌缺血总负荷的关系。方法：随机收集90例不稳定型心绞痛患者及90例稳定型心绞痛患者,观察高同型半胱氨酸血症与心肌缺血总负荷的关系。结果：不稳定型心绞痛组血同型半胱氨酸水平和心肌缺血总负荷显著高于稳定型心绞痛组（P〈0．05）。稳定型心绞痛患者高同型半胱氨酸血症者,其心肌缺血总负荷高于同型半胱氨酸正常组（P〈0．05）。不稳定型心绞痛组高同型半胱氨酸血症患者,其心肌缺血总负荷也明显高于血同型半胱氨酸正常者（P〈0．01）。结论：高同型半胱氨酸血症与心绞痛患者心肌缺血总负荷增加有关联。     

Influence of combined methionine synthase (MTR 2756A > G) and methylenetetrahydrofolate reductase (MTHFR 677C > T) polymorphisms to plasma homocysteine levels in Korean patients with ischemic stroke

PURPOSE: Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case- control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. MATERIALS AND METHODS: DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p=0.04 for MTR, p=0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p= 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p=0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p=0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. CONCLUSION: The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke.     

高同型半胱氨酸血症与缺血性脑血管病危险因素的关系及干预治疗

目的探讨高同型半胱氨酸血症（HHcy）与缺血性脑血管病危险因素的关系及干预治疗。方法选择265例急性缺血性脑血管病患者（其中腔隙性脑梗死85例,短暂性脑缺血发作53例,急性脑梗死127例）和140例对照,检测所有受试者空腹血浆同型半胱氨酸（Hcy）水平并与其它缺血性脑血管病危险因素进行比较。分析HHcy伴有传统危险因素时对缺血性脑血管病的影响,并进一步提出干预治疗措施及预后。结果 HHcy合并高血压病、糖尿病危险因素者可促使缺血性脑血管病的发生（P〈0.01）。使用单一维生素治疗6周无效（P〉0.05）,联合使用两种维生素治疗4-6周起效（P〈0.05）,但尚未达标,联合使用三种维生素治疗2周开始起效（P〈0.05）,4-6周达标,且随访观察1.5年,三种维生素治疗组再发缺血性脑血管病明显减少。结论 HHcy可能与缺血性脑血管病其它危险因素如高血压、糖尿病相互作用促进缺血性脑血管病的发生有关。三种维生素干预治疗4-6周,效果及预后明显优于未服维生素治疗组、一种或两种维生素治疗组。     

2型糖尿病患者高同型半胱氨酸血症与早期肾脏疾病的相关性

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)住院患者高同型半胱氨酸血症对早期肾脏疾病患病风险的影响。方法本研究为回顾性研究。选取南京江北医院2020年10月至2022年6月收住的T2DM患者306例。根据糖尿病肾脏疾病(diabetic kidney disease,DKD)诊断标准分为单纯T2DM组(n=252)和早期DKD组(n=54),比较两组临床资料。结果T2DM患者早期肾脏疾病患病率为17.6%。与单纯T2DM组相比,早期DKD组年龄较大、糖尿病病程较长、同型半胱氨酸水平较高、高同型半胱氨酸血症和高血压占比较大,差异有统计学意义(均P<0.05)。多因素Logistic回归分析显示,高同型半胱氨酸血症使T2DM患者早期肾脏疾病患病风险显著增加5.361倍(OR:6.361,95%CI:3.043-13.296,P<0.05),且同型半胱氨酸水平与T2DM早期肾脏疾病患病风险呈剂量-反应关系,同型半胱氨酸水平每增加1μmol/L,T2DM早期肾脏疾病患病风险增加14.1%(OR:1.141,95%CI:1.061-1.227,P<0.05)。结论T2DM患者高同型半胱氨酸血症显著增加早期肾脏疾病的患病风险,且同型半胱氨酸水平与早期肾脏疾病患病风险增加呈剂量-反应关系。