ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss

AIM: To assess the association between polymorphisms in angiotensin converting enzyme and methylene tetrahydrofolate reductase genes and recurrent pregnancy loss by a case-control study in South Indian women. METHODS: DNA was extracted from peripheral blood leukocytes of 104 women with Recurrent Pregnancy Loss (RPL) and 120 controls. Genotyping of ACE Insertion Deletion and MTHFR C677T polymorphism were carried out by PCR and PCR-RFLP, respectively. RESULTS: No statistically significant difference was observed in the distribution of genotypes between cases and controls for ACE and MTHFR polymorphisms. Further, the combination of MTHFR and ACE genotypes failed to reveal an association. CONCLUSION: In conclusion, the present study reveals lack of association of MTHFR C677T and ACE I/D polymorphisms in RPL in South Indian women. However, we cannot exclude the possibility that other polymorphisms of ACE and MTHFR genes could be associated with the disease and might be clinically useful as a marker to assess risk for RPL.     

Association of the methylenetetrahydrofolate reductase (MTHFR) gene variant C677T with serum homocysteine levels and the severity of ischaemic stroke: a case–control study in the southwest of China

ObjectiveTo determine whether the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is linked to the risk of ischaemic stroke and circulating homocysteine (Hcy) levels in a Chinese population.MethodsThis case–control study recruited angiogram-diagnosed patients with ischaemic stroke and healthy control subjects. The plasma Hcy concentrations were measured and the MTHFR C677T gene polymorphism was genotyped. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the ischaemic stroke.ResultsThis study recruited 198 patients with ischaemic stroke and 168 controls. The TT genotype conferred a higher risk for ischaemic stroke than the CC genotype (odds ratio of 3.563; 95% confidence interval [CI] 1.412, 4.350). The T allele was the predisposing allele for ischaemic stroke. Hcy had an area under the receiver operating characteristic (ROC) curve of 0.624 (95% CI 0.530, 0.758). The ROC for Hcy demonstrated its usefulness in predicting ischaemic stroke. Hcy levels were not associated with ischaemic stroke severity as measured by the NIHSS.ConclusionThe MTHFR C677T gene polymorphism affects circulating Hcy levels. The MTHFR C677T gene polymorphism and hyperhomocysteinaemia may play important roles in predicting the risk of ischaemic stroke.     

西安地区汉族亚甲基四氢叶酸还原酶的两种基因多态性

目的：了解西安地区汉族人MTHFR基因C677T和A1298C两个位点的遗传多态性．方法：应用聚合酶链反应-限制性片段长度多态性(PCR—RFLP)调查西安地区96个汉族人的基因型分布．结果：677T等位基因的分布频率为45％，TT纯合子占18％；1298C等位基因的分布频率为20％．CC合子占3％；双杂合子677CT，1298AC占21％．结论：调查显示这两个位点的遗传多态性与献报道不同，可能具有群体差异性．     

亚甲基四氢叶酸还原酶基因C677T多态性与偏头痛的相关性研究

目的 探讨哈尔滨地区汉族人群中偏头痛患者亚甲基四氢叶酸还原酶(methylenetetrahydrofolate re-ductase,MTHFR)基因C677T位点多态性与偏头痛的相关性.方法 研究包括182例偏头痛患者(有先兆偏头痛43例,无先兆的偏头痛患者139例);健康对照103例.应用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)方法检测MTHFRC677T.基因型.采用x2检验,t检验对实验结果进行统计分析.结果 (1)MTHFR基因型分布在病例组和对照组之间差异无统计学意义(P＞0.05);病例组与对照组间等位基因频率分布差异无统计学意义(P＞0.05).(2)偏头痛临床特征在野生型和突变型之间,在起病年龄、病程、头痛频率、头痛程度、有无先兆症状方面比较差异无统计学意义(P＞0.05),而在疼痛持续时间、伴随症状方面比较差异有统计意义(P＜0.05).结论 本研究显示:(1)MTHFR基因C677T位点多态性可能与哈尔滨地区汉族人群偏头痛的发病无相关性.(2)在哈尔滨地区汉族人群偏头痛患者中,MTHFR基因突变型(CT、TT型)与起病年龄、病程、头痛频率、头痛程度、有无先兆症状无相关性,而与头痛发作持续时间、伴随症状可能具有相关性.     

Association of Methylenetetrahydrofolate Reductase Gene 677C>T Polymorphism with Hypertension in Older Women in a Population of Buenos Aires City

We examined the relationship between the 677C >T polymorphism in the MTHFR gene and tHcy in normotensive (NT) and hypertensive (HT) subjects and the influence of sex and age in a cross-sectional study. Smoking habits, history of vascular disease, diabetes, and tHcy were significantly associated with T allele as hypertension risk factors. The T allele was significantly related with higher tHcy in (i) men versus women (P < .01), (ii) men and women older than 47 years versus the younger ones (P < .05 and P < .001, respectively), (iii) HT women versus NT women (P < .01), and (iv) older HT women versus older NT women (P < .01). We found an association between the 677C>T MTHFR polymorphism and tHcy with hypertension that in women is manifested with age.     

Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes

They‐They TP, Nadifi S, Rafai MA, Battas O, Slassi I. Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes.
Acta Neurol Scand: 2011: 123: 105–110.
© 2010 John Wiley & Sons A/S. Background – The role for the methylenetetrahydrofolate reductase C677T gene variants in the risk of ischemic stroke is controversial. Method – This first case–control study including 91 cases affected by ischemic stroke and 182 controls matched for age, sex, and same area was conducted in Casablanca, Morocco. Allele and genotype frequency were characterized by using PCR followed by HinfI enzymatic digestion. Results – We found no statistic association of T allele carriers genetic factors with stroke; odds ratio, 1.1; 95% confidence interval (CI), 0.59–2.04, P = 0.303. The results shown significant association of T allele carriers genetic factors with atherothrombotic subtype stroke (n = 42); odds ratio, 2.1; 95% CI: 1.17–3.8; P = 0.012, and adjusted odds ratio of 6.5; 95% CI: 1.86–23.1, P = 0.003, for TT genotype variant compared with CC wild genotype. Conclusion – We suggested that MTHFR C677T variant may be a determinant of atherothrombotic event of ischemic stroke in Morocco.     

Association of MTHFR gene polymorphism C677T with susceptibility to late-onset alzheimer’s disease

Increased total plasma homocysteine (t-Hcy) levels are found to be associated with Alzheimer's disease (AD). Because the methylenetetrahydrofolate reductase (MTHFR) gene encodes a key enzyme that influences the metabolism of homocysteine, it has been considered as a possible genetic risk factor for AD. Although the MTHFR gene C677T polymorphism has a significant impact on reducing enzyme activity and increasing t-Hcy concentrations, the association between the C677T polymorphism and AD remains inconclusive. To determine whether the MTHFR gene C677T polymorphism contributes to the risk for late-onset AD (LOAD) in Chinese, we have investigated 104 sporadic LOAD patients and 130 healthy controls. The strong associations of the TT genotype and T-allele with LOAD (p 0.001, OR 5.73 95% CI 1.85-17.72, and p 0.002, OR 1.89 95% CI 1.25-2.86) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon4) status, increased LOAD risks associated with the TT genotype only in the APOE epsilon4 noncarriers (chi2=8.92, df=1, p=0.003) and with the T-allele in either group (chi2=5.18, df=1, p=0.023 and chi2=5.53, df=1, p=0.019) were seen. These results suggest that as an APOE epsilon4 allele-dependent risk factor, the MTHFR gene C677T polymorphism is involved in developing LOAD in Chinese.     

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor

Objectives: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. Methods and results: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (ΔDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P VALUE=0.0076 for DBP, and P VALUE=0.0005 for ΔDBP). We further divided all patients into three groups based on the tertiles of the ΔBP distribution. Compared to subjects in the lowest tertile of ΔDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. Conclusions: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.     

Folic acid: neurochemistry, metabolism and relationship to depression

The associations of folic acid and its derivatives with depressive disorder are reviewed. Derivatives of folic acid such as biopterins and the synthesis of S-adenosyl methionine (SAM) are known either to be associated with improvement or to have a direct therapeutic effect in depressive disorder. Studies investigating plasma and red cell folic acid levels in depressed patients have used differing assay methodologies which make comparison difficult, although there is substantial evidence of the association between depressive disorder (particularly severe depression) and low folic acid levels. The few studies available suggest folic acid has either antidepressant properties or can act as an augmenting agent for standard antidepressant treatment. A recently discovered genetic variant (5,10 MTHFR) leading to altered folic acid metabolism may explain why some individuals are vulnerable to the effects of folic acid deficiency, despite adequate intake. The links of 5,10 MTHFR to the presence of depressive disorder in the community are being investigated.