北京地区汉族人群MTHFR C677T基因多态性分析

目的探索北京地区汉族MTHFR基因多态性分布特征,荟萃(meta)分析北京地区与北方其他地区MTHFR基因多态性分布差异。方法用PCR-金磁微粒层析法检测MTHFR C677T基因,回顾性分析北京协和医院2014年9月至2018年5月3 945例体检健康者MTHFR基因多态性分布特征。查阅中外文献数据库,并对北京地区与北方其他地区汉族的MTHFR基因多态性分布比较。结果北京地区体检健康人群男性MTHFR C677T基因CC、CT和TT基因型频率分别为23.3%,50.5%和26.2%,C、T等位基因频率分别为48.6%和51.4%。女性人群MTHFR C677T基因CC、CT和TT基因型频率分别为22.7%,49.4%和27.9%,C、T等位基因频率分别为47.4%和52.6%,男、女性基因型频率与等位基因频率差异无统计学意义(P0.05)。北京地区体检人群MTHFR C677T基因CC、CT和TT基因型频率与等位基因频率均与黑龙江、吉林、河北、山东和河南等省差异有统计学意义(P0.01)。结论北京地区体检人群MTHFR C677T基因多态性在男、女性人群中的分布无差异;北京地区MTHFR基因分布有自身特点。     

Association of the C677T polymorphism in the MTHFR gene with migraine: a meta-analysis

There are conflicting data concerning the association between migraine and C677T polymorphism of the MTHFR gene. The C677T polymorphism reduces enzymatic capability by 50% and causes hyperhomocysteinaemia. We performed a meta-analysis of all published studies investigating the association between the MTHFR gene and migraine. Pooled odds ratios (OR) were estimated using random (RE) and fixed effects (FE) models. Among the overall 2961 migraineurs there was no significant difference compared with controls. Only in migraine with aura was the TT genotype associated with a higher risk of disease compared with the CC genotype [FE OR 1.30, 95% confidence interval (CI) 1.06, 1.58; RE OR 1.66, 95% CI 1.06, 2.59]. In the same subgroup a significant difference was observed in the comparison between TT and CT + CC genotypes (FE OR 1.32, 95% CI 1.10, 1.59; RE OR 1.63, 95% CI 1.10, 2.43). This study provides evidence for an association of the MTHFR gene only in migraine with aura.     

MTHFR 677C>T polymorphism and cluster headache

(Headache 2011;51:201‐207) Background.— An association between the 677C>T polymorphism (rs1801133) in the methylenetetrahydrofolate reductase gene (MTHFR) and cluster headache is plausible, but has not been investigated. Objective.— To investigate this association among Caucasians. Methods.— Case–control study among 147 cluster headache patients and 599 population‐based age‐ and gender‐matched controls. Cluster headache was diagnosed according to the criteria of the International Headache Society. Genotypes of the MTHFR 677C>T polymorphism were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between cluster headache and genotypes with additive, dominant, and recessive models. We considered a Bonferroni‐corrected P value <.004 as significant. Results.— Mean age at study entry among patients was 44.9 years (SD 11.4), of whom 76.2% were men. The genotype distribution among controls and patients was in Hardy–Weinberg equilibrium. The genotype and allele distribution did not differ between patients with any cluster headache and controls. We also did not find an association when assuming additive, dominant or recessive genetic models. When we looked at subgroups, the effect estimates suggested an increased risk for chronic cluster headache (dominant model: odds ratio = 2.82; 99.6% confidence interval = 0.72‐11.07; P = .03). Conclusions.— Data from our case–control study do not indicate an association between genotypes of the MTHFR 677C>T polymorphism and cluster headache overall. Subgroup analyses suggested that carriers of the MTHFR 677T allele may have an increased risk for chronic cluster headache. This may be regarded as hypothesis‐generating and should be further investigated in independent studies.     

妊娠高血压综合征患者MTHFR基因C677T多态性与Hcy及肾功能指标的相关性研究

目的探讨妊娠高血压综合征(简称妊高征)患者5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与同型半胱氨酸(Hcy)、肾功能指标的相关性。方法纳入妊高征患者86例(疾病组,根据疾病严重程度,进一步分为妊娠高血压组、轻度子痫前期组、重度子痫前期组3个亚组),同时纳入健康妊娠女性200例(正常妊娠组)和健康非妊娠女性150例(健康对照组),采集研究对象的血液标本进行Hcy、尿酸(UA)、肌酐(Cr)及尿素氮(BUN)水平检测,并进行分析。此外,对86例妊高征患者的MTHFR基因进行测序,利用Chromas软件对测序结果跟健康人群进行比对,找出多态性位点进行分析。结果与健康对照组、正常妊娠组相比,疾病组Hcy、UA、Cr及BUN水平均明显升高(P<0.05),且以上指标在重度子痫前期组明显升高(P<0.05)。MTHFR C677T基因型与Hcy具有相关性(P<0.05),Hcy在TT基因型患者中的水平高于CC基因型和CT基因型患者(P<0.05)。结论Hcy及肾功能指标可作为妊高征辅助诊断及病情监测的重要指标,MTHFR基因C677T多态性的检测可为妊高征患者病情严重程度及预后判断提供一定依据,为发现妊高征高危人群提供新思路。     

CXCL12 rs1801157 polymorphism in patients with breast cancer,hodgkin's lymphoma,and non‐hodgkin's lymphoma

Chemokines and their receptors regulate the trafficking of immune cells during their development, inflammation, and tissue repair. The single‐nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12‐A/ stromal cell‐derived factor‐1 (SDF1)‐3′A) in CXCL12/SDF1 gene was assessed in breast cancer, Hodgkin's lymphoma (HL), and non‐Hodgkin's lymphoma (NHL), since the chemokine CXCL12, previously known as SDF1, and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis, and metastasis of different types of tumors. Genotyping was performed by PCR‐RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using a restriction enzyme HpaII cleavage. No significant difference was observed in genotype distribution between breast cancer patients (GG: 57.3%; GA: 39.8%; AA: 2.9%) and healthy female controls (GG: 62.9%; GA: 33%; AA: 4.1%) nor between HL patients (GG: 61.1%; GA:27.8%; AA: 11.1%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%), whereas a significant difference was observed in genotype distribution between NHL patients (GG: 51.4%; GA: 47.1%; AA: 1.5%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%). Further studies will be necessary to elucidate the cancer chemokine network. However, this study suggests that CXCL12 rs1801157 polymorphism may have important implications in the pathogenesis of NHL. J. Clin. Lab. Anal. 23:387–393, 2009. © 2009 Wiley‐Liss, Inc.     

Search for correlations between genotypes and electrophysiological patterns in migraine: the MTHFR C677T polymorphism and visual evoked potentials

Interictally, migraineurs have on average a reduction in habituation of pattern-reversal visual evoked potentials (PR-VEP) and in mitochondrial energy reserve. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and its C677T polymorphism may be more prevalent in migraine. The aim of this study was to search in migraineurs for a correlation between the MTHFR C677T polymorphism and the PR-VEP profile. PR-VEP were recorded in 52 genotyped migraine patients: 40 female, 24 without (MoA), 28 with aura (MA). Among them 21 had a normal genotype (CC), 18 were heterozygous (CT) and 13 homozygous (TT) for the MTHFR C677T polymorphism. Mean PR-VEP N1-P1 amplitude was significantly lower in CT compared with CC, and tended to be lower in TT with increasing age. The habituation deficit was significantly greater in CC compared with TT subjects. The correlation between the cortical preactivation level, as reflected by the VEP amplitude in the first block of averages, and habituation was stronger in CC than in CT or TT. The MTHFR C677T polymorphism could thus have an ambiguous role in migraine. On one hand, the better VEP habituation which is associated with its homozygosity, and possibly mediated by homocysteine derivatives increasing serotoninergic transmission, may protect the brain against overstimulation. On the other hand, MTHFR C677T homozygosity is linked to a reduction of grand average VEP amplitude with illness duration, which has been attributed to brain damage.     

MTHFR 677C>T and ACE D/I Polymorphisms in Migraine: A Systematic Review and Meta‐Analysis

(Headache 2010;50:588‐599) Background.— Data on the association between the MTHFR 677C>T and ACE D/I polymorphisms and migraine including aura status are conflicting. Objective.— The objective of this study is to perform a systematic review and meta‐analysis on this topic. Methods.— We searched for studies published until March 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies and reviews on the topic. Assessment for eligibility of studies and extraction of data was performed by 2 independent investigators. For each study we calculated the odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs. Results.— Thirteen studies investigated the association between the MTHFR 677C>T polymorphism and migraine. The TT genotype was associated with an increased risk for any migraine, which only appeared for migraine with aura (pooled OR = 1.48, 95% CI 1.02‐2.13), but not for migraine without aura. Nine studies investigated the association of the ACE D/I polymorphism with migraine. The II genotype was associated with a reduced risk for migraine with aura (pooled OR = 0.71, 95% CI 0.55‐0.93) and migraine without aura (pooled OR = 0.84, 95% CI 0.70‐0.99). Results for both variants were driven by studies in non‐Caucasian populations. Results among Caucasians did not suggest an association. Extractable data did not allow investigation of gene–gene interactions. Conslusions.— The MTHFR 677TT genotype is associated with an increased risk for migraine with aura, while the ACE II genotype is protective against both migraine with and without aura. Results for both variants appeared only among non‐Caucasian populations. There was no association among Caucasians.     

MTHFR基因677C/T和血清同型半胱氨酸水平与非酒精性脂肪性肝病的相关性

目的 探讨MTHFR基因677C/T和血清同型半胱氨酸(Hcy)水平与非酒精性脂肪性肝病(NAFLD)的相关性.方法 纳入249例成人住院患者,参照NAFLD亚洲诊断标准将其分为NAFLD组(131例)和对照组(118例).采集两组患者的基本资料并检测Hcy水平和MTHFR基因分型,行Hardy-Weinberg遗传平...     

桂东南地区2型糖尿病肾病与 MTHFR 基因 C677T 多态性的相关性

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病（DN）的关系。方法应用聚合酶链反应-限制性片段长度多态性的方法,检测桂东南地区2型糖尿病患者163例 MTHFR 基因 C677T 多态性,其中 DN 82例、单纯糖尿病（DM）81例和健康对照组（CON）77例。同时检测血清同型半胱氨酸（Hcy）水平,并比较各组间 MTHFR 基因型频率、等位基因频率和 Hcy 水平。结果DN 组 MTHFR 基因纯合基因型（TT）、杂合基因型（CT）及 T 等位基因频率（分别为4．9％、37．8％和23．8％）均明显高于 DM 组（分别为2．5％、28．4％和16．7％）和 CON 组（分别为0．0％、29．8％和14．9％）,基因型和等位基因频率分布差异均有统计学意义（P ＜0．05）,而 DM 组和 CON 组之间的分布差异无统计学意义（P ＞0．05）。单因素 Logistic 回归分析结果显示,MTHFR 基因型 C677T 多态性与 DN 的发生密切相关（OR 值及其95％CI 分别为1．660、1．038和2．655）。携带T 等位基因患者血中 Hcy 水平显著高于未携带 T 等位基因患者,差异有统计学意义（P ＜0．01）。结论MTHFR 基因 C677T 多态性与桂东南地区2型糖尿病患者 DN 相关,MTHFR T 等位基因可能是该地区 DN 的易感基因。     

华南地区汉族人群亚甲基四氢叶酸还原酶基因多态性分析

目的了解亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性在华南地区汉族健康人群、原发性高血压患者和高血压合并冠心病患者中的分布情况。方法采用芯片技术对359例人群的MTHFR C677T基因多态性进行检测,并统计男女间基因型频率的差异。结果野生型CC最多见占54.9%,突变型CT占33.1%和TT占12.0%,野生型与突变型在男女人群间的分布差异有统计学意义(P0.05);TT的频率在高血压合并冠心病患者与健康人群和原发性高血压患者中分布差异均有统计学意义(P0.05)。结论 MTHFR C677T的多态性分布在男女人群间有差异,也与原发性高血压患者冠心病的发生相关。     

Distinct association of SLC19A1 polymorphism -43T>C with red cell folate levels and of MTHFR polymorphism 677C>T with plasma folate levels

OBJECTIVES: The role of SLC19A1 -43T>C, MTHFR 677C>T and MS 2756A>G polymorphisms on red cell and plasma folate levels. DESIGN AND METHODS: Genotype analysis of the three polymorphisms. Red cell and plasma folate measurements in 64 patients with coronary artery disease. RESULTS: The non-wild type allele of SLC19A1 polymorphism -43T>C was associated with low red cell folate levels and the non-wild type allele of MTHFR polymorphism 677C>T with low plasma folate levels. CONCLUSION: SLC19A1 and MTHFR genes are differently associated with red cell and plasma folate levels.     

Predictive factors for inadequate stem cell mobilization in Chinese patients with NHL and HL: 14-year experience of a single-center study

Background: Factors affecting progenitor cell mobilization in patients with non‐Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) are incompletely understood. The aim of this retrospective study was to determine which factors are crucial for effective mobilization and collection of autologous peripheral blood stem cells (PBSC) prior to transplantation in Chinese patients. Patients and methods: A total of 239 patients with lymphoma (198 NHL and 41 HL patients) underwent PBSC collection after mobilization with granulocyte‐colony‐stimulating factor (G‐CSF) or G‐CSF plus chemotherapy priming. Results: Patient characteristics at diagnosis and transplant, including low Eastern Cooperative Oncology Group score (P = 0.013), lack of extranodal invasion (P = 0.034), previously administered radiotherapy regimens (P = 0.040), treatment with platinum prior to mobilization (P = 0.042), previous chemotherapy regimens (P = 0.001) and cycles (P < 0.001), and chemotherapy regimens (P < 0.001) were statistically significant for successful mobilization in multivariate analysis. Premobilization factors, including previous radiotherapy (P = 0.009), previous chemotherapy regimens (P = 0.043) and cycles (P = 0.039), low platelet count prior to mobilization (P = 0.042), and lower CD34+ cells in peripheral blood (PB) (P = 0.050) or bone marrow (BM) (P = 0.007) were considered possibly predictive of poor mobilization. We found the patients who had chemosensitive lymphoma had worse progress‐free survival (PFS) than the patients with initial treatment and high risks (P = 0.017). Conclusion: Our analysis showed that high amounts of chemotherapy, radiotherapy, low platelet count, chemosensitive recurrent patients, combination chemotherapy plus G‐CSF and low CD34+ cells in BM prior to mobilization could emerged as important predictive factors for mobilization failure in Chinese patients with NHL and HL. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.     

Methylenetetrahydrofolate reductase C677T gene polymorphism and the association with dyslipidemia in type 2 diabetic Palestinian patients

BackgroundDyslipidemia in diabetes is common and characterized by hypertriglyceridemia with decreased levels of high‐density lipoprotein. The objective of this study was to assess the prevalence of MTHFR C677T polymorphism in Palestinian T2DM patients and to investigate the association between this polymorphism and lipid profile in diabetic patients with and without dyslipidemia.MethodsA total of 208 T2DM patients including 98 with dyslipidemia and 110 without dyslipidemia were enrolled in this study. The MTHFR C677T genotyping was conducted by PCR‐RFLP followed by agarose gel electrophoresis.ResultsThere were no significant differences in either the genotype distribution or allele frequency in T2DM patients with or without dyslipidemia (37.8% CC, 54% CT, 8.2% TT vs. 48.2% CC, 41.8% CT, 11% TT; p = 0.209). However, among the dyslipidemic group, the TT carriers have a higher HDL level (46.8 ± 17.8) compared to (CC+CT) carriers (34.68 + 11.9) (p = 0.01). In the group without dyslipidemia, there was a significant elevation in diastolic blood pressure (DBP) among the CC carriers (83.6 ± 10.6) compared to those who carried at least one mutant allele (CT+TT) (78.1 ± 11.1) (p = 0.009).ConclusionsThe study shows that in our Palestinian population the MTHFR 677TT genotype lowers DBP significantly in patients without dyslipidemia and is related to increased level of HDL in diabetic dyslipidemia patients.     

河南汉族人群静脉血栓栓塞症与MTHFR rs1801131基因多态性的关系

目的探讨亚甲基还原酶(methylenetetrahydrofolate reductase, MTHFR)rs1801131基因多态性与河南地区汉族人群静脉血栓栓塞症(venous thromboembolism, VTE)发生的关系。方法 54例VTE患者为VTE组,54例体检健康者为对照组;应用PStar高通量位点测序技术分析2组MTHFR rs1801131基因多态性,比较2组基因型分布频率和等位基因频率,并进行遗传学平衡定律检测。结果 2组基因型分布均符合遗传学平衡定律;VTE组MTHFR rs1801131基因型GG、GT、TT分布频率分别为0、9.3%、90.7%,等位基因G、T频率分别为4.6%、95.4%;对照组基因型GG、GT、TT分布频率分别为1.9%、33.3%、64.8%,等位基因G、T频率分别为18.5%、81.5%;VTE组TT基因型分布频率、T等位基因频率高于对照组(P<0.05)。结论位于MTHFR基因第1298位点的TT基因多态性可能与河南地区汉族人群中VTE发生有关,等位基因T携带者患静脉血栓的风险更高。     

Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wall

BACKGROUND: The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. MATERIALS AND METHODS: The autopsy study included 123 subjects (90 males and 33 females) aged 18-93. For the light microscopy, a 0.5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. RESULTS: The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2.02 +/- 2.25 vs. 2.53 +/- 1.89, P < 0.04 and 0.56 +/- 1.09 vs. 1.82 +/- 2.66, P < 0.02, respectively). The trend was similar for the coeliac and the right renal arteries. CONCLUSIONS: Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL.     

Opposite impact of Methylene tetrahydrofolate reductase C677T and Methylene tetrahydrofolate reductase A1298C gene polymorphisms on systemic inflammation

Background

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been found to be related with many diseases. Systemic inflammation is now considered as a major predisposition factor for diseases including diabetes mellitus (DM), coronary arterial disease (CAD), stroke, and cancer. This study aimed to investigate whether systemic inflammation is a possible underlying pathogenesis for MTHFR gene polymorphism‐related disease.

Methods

A total of 292 patients were enrolled, and single nucleotide polymorphisms for MTHFR C667T and A1298C were genotyped. Systemic inflammation markers, neutrophil‐to‐lymphocyte ratio (NLR), and platelet‐to‐lymphocyte ratio (PLR) were collected.

Results

In our study population, MTHFR 677 variants had significant higher NLR level than MTHFR 677 wild type (3.77 ± 0.26 vs 3.06 ± 0.18, P = .028). Logistic regression analysis showed that MTHFR 677 variants were significantly associated with increased NLR level. MTHFR 1298 variants showed the opposite effects which tended to have lower level of NLR (3.21 ± 0.16 vs 3.79 ± 0.34, P = .087) and PLR (137.0 ± 4.8 vs 157.7 ± 9.4, P = .052) than MTHFR 1298 wild type. General linear model showed that there was no statistically significant interaction between MTHFR C667T and A1298C gene polymorphism on NLR or PLR.

Conclusions

This study indicates that MTHFR C677T and MTHFR A1298C gene polymorphisms have opposite effect on systemic inflammation, and systemic inflammation may contribute to the pathogenesis for diseases associated with MTHFR C667T gene polymorphism.