A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine/methionine metabolism. The most-studied C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C) has also been reported to lower enzyme activity. Whether A1298C is a risk factor for coronary artery disease, separately or in combination with C677T, and/or relative to total plasma homocysteine and folate status, is unclear to date. We evaluated this hypothesis in 470 angiographically characterized subjects, 302 with coronary artery disease, and 168 with normal coronary arteries. The frequency of the 1298C allele was 0.33 and that of combined heterozygosity 0.315. No difference was found in the frequency of the genotypes or when analyzed for combined heterozygosity between patients with coronary artery disease and normals. Independent of folate status, the 1298C allele was not associated with increased total plasma homocysteine. No additional effect of A1298C on total plasma homocysteine was observed in 148 combined heterozygotes compared with 98 heterozygotes for the C677T alone. These findings do not support a major role for the A1298C mutation in homocysteine metabolism and emphasize the hypothesis that MTHFR genotypes may interfere with coronary artery disease risk only when an unbalanced nutritional status leads to raised total plasma homocysteine levels.     

MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis

MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.     

亲代MTHFR基因677C/T多态性与子代非综合征性唇腭裂的相关性

目的 探讨山东地区亲代亚甲基四氢叶酸还原酶( methylenetetrahydrofolate reductase,MTHFR)基因677C/T多态性与子代发生非综合征性唇腭裂(nonsyndromic cleft lip with or without cleft palate,NSCL/P)的关联.方法 应用聚合酶链反应-限制性片段长度多态性分析技术(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)对2006年8月至2008年8月在齐鲁医院治疗的89对NSCL/P患者亲代和64对健康查体儿童亲代的MTHFR基因677C/T多态性进行检测.结果 患者母亲与正常儿童母亲的T等位基因频率分别为65.73％和46.09％,C等位基因频率分别为34.27％和53.91％,其构成比差异有统计学意义(x2=13.663,P＜0.01);携带T等位基因的母亲子代患NSCL/P的风险为未携带T等位基因的母亲子代的2.243倍(95％CI:1.408～3.572).患者的父亲与正常儿童父亲的T等位基因频率分别为62.92％和55.47％ ;C等位基因频率分别为37.08％和44.53％,其构成比差异无统计学意义(x2 =2.222,P＞0.05);病例组和对照组后代可能为纯合突变胎儿的机率分别为43％和29％(P＞0.05).结论 山东地区母亲的MTHFR基因677C/T突变对后代NSCL/P的发生有重要的影响;父亲的MTHFR基因677C/T突变则可能不是子代患NSCL/P的风险因素.     

Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.     

Analysis of the MTHFR 1298A-->C and 677C-->T polymorphisms as risk factors for neural tube defects

The thermolabile variant (677TT) of methylenetetrahydrofolate reductase (MTHFR) is a known risk factor for neural tube defects (NTDs). The relationship between a second MTHFR polymorphism (1298A→C) and NTD risk has been inconsistent between studies. We genotyped 276 complete NTD triads (mother, father and child affected with an NTD) and 256 controls for MTHFR 1298A→C. Our findings do not support a role for the 1298A→C polymorphism in NTDs (OR 0.85 (95% CI 0.49–1.47), p= 0.55), nor do we observe a combined effect with the 677C→T polymorphism. Electronic Publication     

Meta analysis of the association between MTHFR C677T polymorphism and the risk of congenital heart defects

Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD). The aim of this study was to investigate the relationship of the MTHFR C677T polymorphism with the risk of CHD in children with CHD and their parents by meta-analysis. Studies were identified by searching electronic literature for papers before 2011, focusing on MTHFR C667T and the risk of CHD. All data were analyzed using the fixed effects model in Cochrane Review Manager 5.1.1. Twenty eligible case-control and family-based studies were included. Overall analysis yielded pooled odds ratios (OR) of 1.55 (95%CI 1.25-1.93), 1.84 (95%CI 1.23-2.74) and 1.20 (95%CI 0.94-1.54) for fetal, paternal and maternal MTHFR TT genotypes in case-control studies, respectively, but yielded a summarized OR of 0.9 (95%CI 0.97-1.12) in family-based studies. Our results suggested that the fetal and paternal MTHFR C667T gene may be associated with an increased occurrence of CHD. Further larger studies should be performed to investigate the interaction between maternal genetic polymorphism, folic acid intake and hyperhomocysteinemia, and the development of CHD.     

同型半胱氨酸和MTHFR基因多态性与Alzheimer病的关系

目的探讨同型半胱氨酸(Hcy)和5,10 亚甲基四氢叶酸还原酶(MTHFR)基因多态性与Alzheimer病的关系.方法运用多聚酶链反应限制性内切酶片段长度多态性技术(PCR RFLP)和荧光偏振法(FPIA)检测66例阿尔茨海默病及143例正常人MTHFR基因多态性和血浆总Hcy水平.结果 (1)AD病人甲基四氢叶酸还原酶基因中,基因型C/T占56.06%,明显高于对照组的34.97%(P<0.01,RR=0.355),C/C占39.39%,明显低于对照组的62.94%(P<0.01),T/T占4.25%,与对照组2.09%无明显差异(P>0.05). AD病人中甲基四氢叶酸还原酶基因等位基因C的频率为67.43%、相对危险率(RR)为0.594,T的频率为32.57%、与对照组的C为80.42%、T为19.58%有显著性差异(P≤0.05).(2)AD病例组与对照组血浆Hcy分别为14.72±6.2μmol/L和10.9±2.4μmol/L,两者差异有显著差异(P<0.05).AD患者血浆总Hcy水平显著高于正常组.结论 MTHFR基因突变及高同型半胱氨酸血症与Alzheimer病发生有一定关系.     

The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis

The association between retinopathy in type 2 diabetes [diabetic retinopathy (DR)] and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in several case-control studies. These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of developing DR whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DR was conducted. Four out of five identified studies included populations of East Asian descent, and only one involved samples from European descent (Caucasians). Overall, the meta-analysis suggested large heterogeneity between studies (p = 0.08, I² = 52%) and marginal association between C677T transition and the risk of developing DR: random effects odds ratio (OR) = 1.39 [95% CI (1.05, 1.83)]. The sensitivity analysis [exclusion of one East Asian study with the controls not in Hardy–Weinberg equilibrium (HWE)] showed no heterogeneity (p = 0.25, I² = 27%) and no significant association: fixed effects OR = 1.22 [95% CI (0.99, 1.51)] and random effects OR = 1.24 [95% CI (0.96, 1.60)]. The sub-group analysis for the East Asian population produced a significant association: fixed effects OR = 1.48 [95% CI (1.20, 1.83)] and random effects OR = 1.52 [95% CI (1.14, 2.03)]. However, sensitivity analysis in East Asians revealed that the association is marginal: fixed effects OR = 1.33 [95% CI (1.04, 1.70)] and random effects OR = 1.36 [95% CI (1.01, 1.83)]. There is a source of bias in the selected studies: the largest studies failed to show association while the smallest study claimed an association. The above findings reinforce the need for larger and more rigourous studies in this area.     

Frequency of the thermolabile variant C677T in the MTHFR gene and lack of association with neural tube defects in the State of Yucatan,Mexico

The C677T variant in the MTHFR gene is considered to be an associated risk factor for neural tube defects. However, the association has not been found in some ethnic groups. In order to assess the association between neural tube defects and the C677T variant, we determined the frequency of this variant in the MTHFR gene in the State of Yucatan, Mexico, where neural tube defects are highly prevalent. The study was performed on 65 subjects with spine bifida, 60 of their mothers and 110 control subjects. The presence of the C677T variant was determined by amplification and digestion with HinF1 of each subject's DNA. Genotypic and allelic frequencies were calculated for all groups. We did not observe any statistically significant difference in the genotypic or allelic frequencies between cases and controls for any of the groups studied (p > 0.05), suggesting that the thermolabile variant C677T is not an associated risk factor neither for the development of neural tube defects nor for mothers to have affected offspring in the population from Yucatan. Interestingly, the frequency of the C677T variant (54%) obtained in the Yucatan population is one of the highest reported (p < 0.01) and confirmed the high frequency of this allele throughout Mexico.     

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。     

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（χ^2=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。     

A low prevalence of the C677T mutation in the methylenetetrahydrofolate reductase gene in Asian Indians

The prevalence of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in Asian Indians from India was determined and the association of the mutant allele with coronary artery disease (CAD) was evaluated in a case-control study. The case group consisted of 251 patients with CAD; 195 male and 56 female aged from 29 to 82 years (mean age +/- SD, 57.5 +/- 10.6 years). The control group consisted of 216 apparently healthy individuals without evidence of CAD; 161 male and 55 female aged from 30 to 83 years (mean age +/- SD, 54.9 +/- 10.4 years). All the patients were assessed by coronary angiography. While 33 patients had normal coronaries, 23, 25 and 39 patients had single-vessel, two-vessel and triple-vessel disease, respectively. Eighty-three patients (33%) had suffered myocardial infarction less than a year to five years earlier. The C677T polymorphism in the MTHFR gene was assessed. While 31% of the controls and 38% of the patients had the heterozygous genotype, 2% of the control group and none of the patients had the mutant homozygous genotype. The overall 'T' allelic frequencies were comparable in control and patient groups (0.18 and 0.19, respectively), but the association of the sum of heterozygous and homozygous genotypes with CAD (1, 2 or 3-vessel disease) was statistically significant for females only [Odds ratio (95% confidence intervals), 2.8 (1.1-6.9), p = 0.023]. No association was found between genotype distribution and previous myocardial infarction or severity of atherosclerosis.     

MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. We aimed to evaluate the association between MTHFR A1298C and C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Eighty-five patients with CML and a control group containing 100 healthy, age and sex matched individuals were examined for MTHFR C677T and A1298C polymorphisms using polymerase chain reaction-restriction fragment-length (PCR-RFLP) method. The frequency of 677TT genotype in patients with CML was significantly higher compared to controls (OR = 2.513, 95% CI: 0.722-4.086, P = 0.025). No such association was shown for heterozygous 677CT (OR = 1.010, 95% CI: 0.460-2.218, P = 0.981). Moreover, for A1298C genotype, a statistically significant higher frequency of 1298CC was also detected in CML patients compared to control group (OR = 1.1816, 95% CI: 0.952-3.573, P = 0.036), 0.036). No such statistical significance was demonstrable for heterozygote 1298AC (OR = 1.046, 95% CI: 0.740-1.759, P = 0.092). In addition, patients with joint 677CT/1298AC or 677TT/1298CC genotypes showed an association with increased risk of CML (OR = 1.849, 95% CI: 0.935-2.540, P = 0.024; OR = 1.915, 95% CI: 1.202-3.845, P = 0.020 respectively). .A statistically significant increased risk of resistant to therapy was observed with 677CT and 1298AC genotypes (P = 0.001, P = 0.002 respectively). We conclude that both MTHFR 677TT and 1298CC polymorphisms have been associated with risk of CML and both 677CT and 1298AC genotypes are associated with higher risk of resistant to therapy.     

Maternal and offspring MTHFR gene C677T polymorphism as predictors of congenital atrial septal defect and patent ductus arteriosus

To observe the association of MTHFR gene C677T locus polymorphism with occurrence of congenital heart defects (CHDs), 21 patients with atrial septal defect (ASD), 35 patients with patent ductus arteriosus (PDA), one patient with both conditions combined, and their biological parents were collected as the case group. Another 104 normal individuals and their biological parents without a family history of birth defects were selected as the control group. MTHFR C677T genotypes of each sample were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed for the occurrence of ASD, the odds ratio (OR) of TT genotype was 4.08 [95% confidence interval (95% CI) = 1.28-13.24] compared with CT genotype. For the occurrence of PDA, the ORs of TT were 3.44 (95% CI = 0.89-16.13) and 2.38 (95% CI = 0.92-6.14) compared with CC and CT genotypes, respectively. Author as meant? Compared with CC + CT genotype combination, the ORs of TT were 3.95 (95% CI = 1.38-11.44) and 2.60 (95% CI = 1.02-6.36) for ASD and PSD respectively. The results also had sex differences and the statistical significance was only observed in male ASD and female PDA. The ORs of T allele carriers were 2.29 (95% CI = 1.08-4.92) and 1.88 (95% CI = 1.02-3.47) compared with C allele for the occurrences of ASD and PDA respectively. The analysis of parents genotype showed that the OR of TT mothers was 2.31 (95% CI = 0.96-5.59, P < 0.05) compared with (CC + CT) for the occurrence of PDA in offspring. So this study could give a clue that MTHFR C677T locus variation was related with occurrence of ASD and PDA, and the carriers of TT genotype and T allele had higher risk of diseases. The mother carrying TT genotype was associated with occurrence of PDA in offspring.     

Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis

To clarify the influence of MTHFR C677T and A1298C polymorphisms on gastric cancer (GC), a meta-analysis of eight case-control studies (1,584/2,785 cases/controls) was carried out. Overall, there was moderate heterogeneity among studies, and the C677T allele T was associated with a 27% increased risk of GC compared with C allele: the random effects (RE) OR (95% confidence interval in parenthesis) was significant [OR=1.27 (1.13–1.44)]. In East Asians, the association was significant: RE OR=1.28 (1.14–1.44), whereas, in Caucasians it was not significant. Regarding gastric cancer adenocarcinoma (GCA), an association for the allele contrast in East Asians was detected: fixed effects (FE) OR=1.36 (1.18–1.56). The recessive model for allele T produced significant results overall and in East Asians for GC [FE OR=1.47 (1.26–1.72) and FE OR=1.61 (1.32–1.96), respectively] and for GCA [RE OR=1.53 (1.13–2.05) and FE OR=1.70 (1.36–2.12)]. The A1298C polymorphism was associated with GCA in East Asians: the FE OR for the allele contrast (C vs. A) was 1.38 (1.18–1.62), and under a recessive model for allele C, OR=1.62 (1.28–2.06). There were no sources of bias in the selected studies; the differential magnitude of effect in large versus small studies was not significant. In conclusion, there is evidence of association between MTHFR polymorphisms and GC, mainly in East Asians.     

Methylenetetrahydrofolate Reductase C677T polymorphism and breast cancer risk in Moroccan women

Background

Methylenetetrahydrofolate (MTHFR) enzyme plays an important role in folate metabolism which is involved in DNA methylation, repair, and synthesis.

Objective

We investigated if the MTHFR C677T polymorphism modulates the risk of developing breast cancer in Moroccan women.

Methods

Genotyping was performed by PCR-RFLP method on a sample of 96 patients with breast cancer and 117 controls.

Results

A positive correlation was found between the MTHFR C677T polymorphism and progesterone receptors expression (p= 0.04). According to menopausal status, the heterozygous CT (OR = 2.29 and P = 0.03) was statistically significant in pre-menopausal women. There was a significant association between C677T polymorphism and breast cancer risk in both additive (OR = 2.2, 95% CI = 1.24–3.86, p = 0.007) and dominant (OR = 2.10, CI 95% = 1.21–3.64, p = 0.008) models. In addition, the T allele were associated with a high breast cancer risk (OR = 1.59, 95% CI = 1.04–2.44, p = 0.03).

Conclusion

In the light of our preliminary study, 677T allele and 677CT MTHFR genotype may represent a genetic determinant increasing breast cancer risk in Moroccan women. A larger study including a larger sample size and more information is needed to confirm our conclusions.     

MTHFR基因C677T多态性与冠心病患者血浆同型半胱氨酸和叶酸水平相关

目的研究宁夏地区汉族人群5,10-亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态性、同型半胱氨酸水平(Hcy)及叶酸水平与冠心病(CHD)的相关性。方法用病例-对照研究方法、应用限制性片段长度多态性扩增技术(PCR-RFLP)分析宁夏地区汉族202例冠心病患者及199例正常人群MTHFRC677T基因型频率及基因频率的分布特点。荧光偏振免疫分析法测定血浆Hcy水平,化学发光免疫分析法测定血清叶酸、VitB12浓度。结果 (1)病例组与对照组MTHFRC677T基因型频率分别为CC型23.3%vs20.7%、CT型52.3%vs54.5%和TT型24.4%vs24.8%,两组间基因型及等位基因频率分布无差异。(2)冠心病患者组中MTHFR基因C677TCC基因型患者血浆Hcy浓度(10.84μmol/L)较T基因携带者(12.24μmol/L)低(P<0.01)。CC基因型患者血浆叶酸浓度(5.38μg/L)较T基因携带者(3.72μg/L)高(P<0.05)。结论 MTHFRC677T的3种基因型频率在宁夏汉族冠心病患者和正常人群中的分布无统计学意义。MTHFR基因C677T多态性与冠心病的危险因素Hc...     

The C677T polymorphism in MTHFR is not associated with migraine in Portugal

Migraine is a debilitating disorder affecting a large proportion of the population. The effect of methylenetetrahydrofolate reductase (GeneID: 4524) polymorphisms in migraine etiology and development has been a theme of great interest. Several populations were evaluated with contradictory results. In this case-control study, we investigated the effect of the C677T polymorphism in MTHFR, as a genetic risk factor for migraine, in the Portuguese population. We observed that, overall, there was no significant difference in the frequencies of MTHFR C677T genotypes or of the T-allele among the Portuguese migraineurs when compared to controls. There was also no association of migraine with aura with MTHFR genotypes or with the T-allele, in contrast with previous studies. Regarding the risk of the T-allele homozygote carriers, there was an equal probability to develop migraine with aura over migraine without aura in our patients. Thus, we conclude that the C677T MTHFR polymorphism, responsible for a reduction of the MTHFR activity in folate metabolism, is not a major genetic susceptibility factor for migraine in the Portuguese population.     

唐氏综合征患儿母亲MTHFR C677T基因多态性及血浆叶酸、同型半胱氨酸水平的研究

目的研究浙南地区汉族妇女叶酸及代谢产物同型半胱氨酸水平、亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多态性与唐氏综合征(Down’s Syndrome,DS)发生的关系。方法对84例已生育DS患儿的母亲(观察组)和120例生育过正常儿童的母亲(对照组)采用PCR扩增及DNA测序法检测亚甲基四氢叶酸还原酶基因MTHFR C677T单核苷酸多态性;免疫发光法检测叶酸(Folate)及循环酶法检测血浆同型半胱氨酸(Hcy)水平。结果 MTHFR 677 T基因及CT、TT基因型的频率两组无统计学意义(P>0.05)。对观察组与对照组的部分标本行血浆Folate与Hcy水平测定,观察组Folate水平显著高于对照组(t=-5.572,P<0.05);Hcy水平两组平均水平无统计学意义(t=0.152,P>0.05);Fo-late与Hcy水平呈负相关关系(r=-0.217,P<0.05)。观察组与对照组MTHFR 677CT、TT基因型与CC基因型Hcy水平比较均无统计学意义(P>0.05),观察组TT基因型Hcy水平比对照组有显著性升高(t=2.546,P<0.05)。结论本研究MTHFR C677T位点不是浙南地区汉族妇女DS的风险因素;DS母亲Folate水平高于对照组及MTHFR 677 TT基因型Hcy水平高于对照组,可能存在影响叶酸代谢的其他相关基因的多态性或营养的缺乏,有待进一步深入研究。     

Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages

The aim of this study was to investigate the relationship between recurrent miscarriages and factor V Leiden, prothrombin G20210A and C677T methylenetetrahydrofolate reductase (MTHFR) mutations. In this case-control study the prevalence of factor V Leiden, prothrombin G20210A and C677T methylenetetrahydrofolate reductase mutations was determined in a consecutive series of 80 recurrent miscarriage patients and 100 controls. Fifteen of 80 recurrent miscarriage patients and four out of 100 controls carried the factor V Leiden mutation (19 versus 4%, P = 0.003, odds ratio 5.5, 95% confidence interval (CI): 1.7-17). Seven of 80 recurrent miscarriage patients and two of 100 controls were carriers of the prothrombin G20210A mutation (9 versus 2%, P = 0.038, odds ratio 4.6, 95% CI: 0.9-23.2). Six of 80 recurrent miscarriage women and 15 of 100 controls were homozygotes for the C677T MTHFR mutation (8 versus 15%, P = 0.134, odds ratio: 0.4, 95% CI: 0.1-1.2). Our results suggest that the presence of factor V Leiden and prothrombin G20210A polymorphism, but not MTHFR C677T homozygosity, could be additional risk factors for recurrent miscarriages. Furthermore, it was suggested that the prevalence of factor V Leiden and prothrombin G20210A mutations is more prominent in second trimester, primary fetal losses and it is independent of the existence of additional pathology predisposing to recurrent fetal losses.