山东地区非综合征性唇腭裂患者MTHFR基因C677T的多态性研究

目的探讨山东地区亚甲基四氢叶酸还原酶(MTHFR)基因C677T的多态性与非综合征性唇腭裂(NSCL/P)的关系。方法运用聚合酶链反应-限制性内切酶片段长度多态性分析技术(PCR-RFLP),对2006年8月至2008年8月曾在齐鲁医院治疗的来自山东地区NSCL/P患儿35例和健康查体的正常儿童51例MTHFR基因的C677T基因型检测分析。结果患者组与对照组的基因型构成比有统计学意义(χ2=8.770,P=0.0121)。对T分析,计算得到携带T等位基因的儿童患非综合征性唇腭裂的危险性是不携带T等位基因儿童的2.568倍(OR=2.568,95%CI:1.324-4.979)。TT突变纯合子患非综合征性唇腭裂的危险性是非TT纯合子的3.095倍(OR=6.088,95%CI:1.240-7.722)。结论 MTHFRC677T的T等位基因可能是山东地区非综合征性唇腭裂的遗传风险因子。     

非综合征性唇腭裂与亚甲基四氢叶酸还原酶基因A1298C相关性的研究

目的 研究亚甲基四氢叶酸还原酶基因(methylenetetrahydrofolate reductase,MTHFR)A1298C多态性与中国华北人群非综合征性唇腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关系.方法 通过聚合酶链反应-限制性片段长度多态性,在158例NSCL/P患者和192名健康对照中,对MTHFR基因A1298C单核苷酸多态性(single nucleotide polymorphism,SNP)rs1801131进行检测.利用拟合优度卡方检验分析基因型分布频率是否符合Hardy-Weinberg平衡定律;应用Unphased软件分析等位基因频率与NSCL/P的相关性.结果 MTHFR基因A1298C多态性基因型频率分布符合Hardy-Weinberg平衡;等位基因和基因型频率在唇裂合并或不合并腭裂组和健康对照组之间差异无统计学意义;基因型分布单纯腭裂(AA 78%、AC+CC 22%)与健康对照组(AA 74%、AC+CC 26%)比较,差异有统计学意义(χ2＝4.256,P=0.039),AC+CC基因型频率健康对照组(26%)高于单纯腭裂组(22%)(OR=0.8,95%CI=0.381～1.683).结论 MTHFR A1298C多态性位点可能与中国人群非综合征性单纯腭裂的发生有关.

Abstract：

Objective To investigate the association between a polymorphism of methylenetetrahydrofolate reductase with Non-syndromic cleft lip with or without cleft palate(NSCL/P)in Chinese population. Methods The polymerase chain reaction (PCR)-based restriction fragment length polymorphism(RFLP)technique was used to detect a single nucleotide polymorphism(SNP), rs1801131, at the methylenetetrahydrofolate reductase(MTHFR)gene in both 158 patients with NSCL/P and 192 healthy individuals. The Hardy-Weinberg equilibrium for genotypic distributions was estimated by the goodness-of-fit test. The UNPHASED program was applied to perform the association analysis. Results The genotypic distribution of A1298C was not deviated from the Hardy-Weinberg equilibrium in both controls and patients. No association was found between cleft lip with or without palate(CL/P)and controls. There was significant difference of cleft palate only(CPO)and the healthy individuals(χ2＝4.256, P=0.039). The frequency of AC+CC genotype was higher in control group than that in CPO group(OR=0.8, 95%CI=0.381-1.683),26 among 100 healthy individuals carried AC+CC genetypes,which were carried by 22% of CPO patients. Conclusions The polymorphism of MTHFR A1298C may be involved in the occurrence of non-syndromic cleft palate only in Chinese population.     

General anesthesia and methylenetetrahydrofolate reductase deficiency

Methylenetetrahydrofolate reductase (MTHFR) deficiency is an autosomal recessive disorder with a spectrum of manifestations including neurological symptoms, premature arteriosclerosis, and venous and arterial thrombosis. Most patients are heterozygous for multiple MTHFR substitutions; small minorities are homozygous for mutations at this locus. Among these mutations, the C677T polymorphism is the most deleterious. Nitrous oxide use in anesthesia leads to significant increases in plasma homocysteine. We present a patient undergoing urgent surgery with a preoperative diagnosis of homozygous MTHFR deficiency.     

亚甲基四氢叶酸还原酶基因C677T多态性与缺血性脑卒中关系的荟萃分析

目的 综合评价亚甲基四氢叶酸还原酶(MTHFR)基因多态性与缺血性脑卒中(IS)在不同种族间的关系.方法 电子检索MEDLINE、EMBASE、Cochrane Library等数据库,查找已发表的相关文献.采用荟萃分析方法,对17篇关于MTHFR基因多态性与缺血性脑卒中关系的研究文献进行综合定量分析.结果 荟萃分析表明,携带MTHFR基因TT基因型发生缺血性脑卒中的危险性是非TT基因型的1.30倍,95%CI为1.11～1.52.携带MTHFR基因CC基因型发生缺血性脑卒中的危险性是非CC基因型的0.88倍,95%CI为0.79～0.98.亚组分析显示MTHFR基因发生缺血性脑卒中的危险性因种族而异,高加索人群更易于发生缺血性脑卒中.结论 MTHFR基因C677T多态性与高加索人缺血性脑卒中的易感性密切相关,与蒙古人及其他人种缺血性脑卒中的关系需进一步研究讨论.

Abstract：

Objective To evaluate the relationship between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the susceptibility of ischemic stroke among different ethnic populations.Methods The databases of MEDLINE, EMBASE, Cochrane Library and others were searched. And a total of 17 studies published in English between 2000 and October 2010 on the association of MTHFR gene C677T polymorphism with ischemic stroke were selected. A comprehensive quantitative analysis was performed by meta-analysis. Results The results showed that the pooled OR values of ischemic stroke with TT and CC genotype were 1.30 (95% CI: 1.11 to 1.52) and 0. 88 (95% CI: 0. 79 to 0. 98 ) respectively. And when sub-grouped by ethnic populations, the Caucasians were more likely than other populations to suffer ischemic stroke. There was a low probability of publication bias. Conclusion The presence of MTHFR TT gene is associated with an elevated risk of developing ischemic stroke, especially in Caucasians.     

亚甲基四氢叶酸还原酶和甲硫氨酸合成酶还原酶基因多态性研究

目的:探讨编码叶酸代谢通路中关键酶的基因多态性与新生儿神经管缺陷(NTDs)间的关联性,及在部分中国女性人群中的分布特征,从而指导孕期叶酸补充和风险监测。方法:采用循证医学方法对5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C和甲硫氨酸合成酶还原酶(MTRR)A66G与NTDs的关联性进行Meta分析,并在中国的北方(山东、河南)和南方(四川、海南)地区进行了1 017例样本的分子流行病学研究。结果:MTHFR C677T位点TT基因型相对于CC型的比值比为3.35(95%CI:1.39～8.13),TT型在北方和南方女性人群中的频率分别为37.35%和10.44%,差异有统计学意义;MTHFR A1298C和MTRR A66G虽然从生物学机制上与NTDs的发生密切相关,但尚需进行大规模的人群研究。结论:基于MTHFR和MTRR多态性检测的孕期叶酸补充指导和监测将是进一步降低新生儿出生缺陷的重要方法。     

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population.Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45).ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.