MTHFR 677C>T Polymorphism Increases the Male Infertility Risk: A Meta-Analysis Involving 26 Studies

Background and Objectives

Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy.

Methods

Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk.

Results

Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23–1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19–1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup.

Conclusions

Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk.     

The 677C>T (rs1801133) Polymorphism in the MTHFR Gene Contributes to Colorectal Cancer Risk: A Meta-Analysis Based on 71 Research Studies

Background

The 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene is considered to have a significant effect on colorectal cancer susceptibility, but the results are inconsistent. In order to investigate the association between the MTHFR 677C>T polymorphism and the risk of colorectal cancer, a meta-analysis was held based on 71 published studies.

Methods

Eligible studies were identified through searching the MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and CNKI database. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with x²-based Q-test. Begg''s and Egger''s test were also carried out to evaluate publication bias. Sensitive and subgroup analysis were also held in this meta-analysis.

Results

Overall, 71 publications including 31,572 cases and 44,066 controls were identified. The MTHFR 677 C>T variant genotypes are significantly associated with increased risk of colorectal cancer. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for CC vs TT (OR = 1.076; 95%CI =  1.008–1.150; I² = 52.3%), CT vs TT (OR = 1.102; 95%CI = 1.032–1.177; I² = 51.4%) and dominant model (OR = 1.086; 95%CI = 1.021–1.156; I² = 53.6%). Asians for CC vs TT (OR  = 1.226; 95%CI  = 1.116–1.346; I²  = 55.3%), CT vs TT (OR  = 1.180; 95%CI  = 1.079–1.291; I²  = 36.2%), recessive (OR  = 1.069; 95%CI  = 1.003-1.140; I²  = 30.9%) and dominant model (OR  = 1.198; 95%CI  = 1.101-1.303; I²  = 52.4%), and Mixed populations for CT vs TT (OR  = 1.142; 95%CI  = 1.005-1.296; I²  = 0.0%). However, no associations were found in Africans for all genetic models.

Conclusion

This meta-analysis suggests that the MTHFR 677C>T polymorphism increases the risk for developing colorectal cancer, while there is no association among Africans found in subgroup analysis by ethnicity.     

B-Type Natriuretic Peptide and Prognosis of End-Stage Renal Disease: A Meta-Analysis

Background

The prognostic importance of B-type natriuretic peptide (BNP) or N-terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial.

Methodology/Principal Findings

We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively.

Conclusions/Significance

BNP/NT-proBNP is a promising prognostic tool to risk-stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors.     

A Meta-Analysis of Mortality in End-Stage Renal Disease Patients Receiving Implantable Cardioverter Defibrillators (ICDs)

Data on the effectiveness of implantable implantable cardioverter defibrillators (ICDs) with respect to reducing mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. The purpose of this meta-analysis was to compare the mortality of patients with ESRD who have received and not received an ICD. A search was conducted on January 31, 2013 of Medline, Cochrane, EMBASE, and Google Scholar. Studies were selected for inclusion based on the following criteria. 1) Randomized controlled trial. 2) ESRD patients with heart failure. 3) Device therapy (ICD, CRT-defibrillator [CRT-D]) used to treat heart failure. 4) Primary outcome is survival analysis. 5) Retrospective study if survival analysis was performed. The primary outcome was overall survival (OS), and the secondary outcome was 2-year survival. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and a χ²-based test of homogeneity was performed. Three studies were included in the analysis. The combined OR for OS was 2.245 (95% CI 1.871 to 2.685, P<0.001), indicating that patients with an ICD had a significantly higher OS than those without an ICD. The combined OR for 2-year survival was 2.312 (95% CI 1.921 to 2.784, P<0.001), indicating that patients with an ICD had a significantly higher 2-year survival rate than those without an ICD. The use of ICD in patients with ESRD is associated with an increase in the OS and the 2-year survival rate.     

MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis

Epidemiological studies have evaluated the association between MTHFR 677C>T and 1298A>C polymorphisms and risk of male infertility. However, the results from the published studies on the association between these two MTHFR polymorphisms and male infertility risk are conflicting. To derive a more precise estimation of association between the MTHFR polymorphisms and risk of male infertility, we performed a meta-analysis. A comprehensive search was conducted to identify all case–control studies of MTHFR polymorphisms and male infertility risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both 677C>T and 1298A>C polymorphisms were not significantly associated with male infertility risk. However, in stratified analysis by ethnicity, we found that the 677C>T polymorphism was significantly associated with the risk of male infertility in Asian population (TT vs. CC: OR = 1.57, 95% CI: 1.05–2.37, P = 0.03; TT vs. TC + CC: OR = 1.40, 95% CI: 1.05–1.86, P = 0.02; TT + TC vs. CC: OR = 1.34, 95% CI: 1.01–1.77, P = 0.04). Although some modest bias could not be eliminated, this meta-analysis suggested that the MTHFR 677T allele might be a low-penetrant risk factor for male infertility, especially in Asian population.     

MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

Background

Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent.

Methods and Results

We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067).

Conclusion

677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer.     

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals

Background

Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.

Methodology/Principal Findings

Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.

Conclusions/Significance

These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene.     

Aberrant Functional Connectome in Neurologically Asymptomatic Patients with End-Stage Renal Disease

Purpose

This study aimed to investigate the topological organization of intrinsic functional brain networks in patients with end-stage renal disease (ESRD).

Materials and Methods

Resting-state functional MRI data were collected from 22 patients with ESRD (16 men, 18–61 years) and 29age- and gender-matched healthy controls (HCs, 19 men, 32–61 years). Whole-brain functional networks were obtained by calculating the interregional correlation of low-frequency fluctuations in spontaneous brain activity among 1,024 parcels that cover the entire cerebrum. Weighted graph-based models were then employed to topologically characterize these networks at different global, modular and nodal levels.

Results

Compared to HCs, the patients exhibited significant disruption in parallel information processing over the whole networks (P< 0.05). The disruption was present in all the functional modules (default mode, executive control, sensorimotor and visual networks) although decreased functional connectivity was observed only within the default mode network. Regional analysis showed that the disease disproportionately weakened nodal efficiency of the default mode components and tended to preferentially affect central or hub-like regions. Intriguingly, the network abnormalities correlated with biochemical hemoglobin and serum calcium levels in the patients. Finally, the functional changes were substantively unchanged after correcting for gray matter atrophy in the patients.

Conclusion

Our findings provide evidence for the disconnection nature of ESRD’s brain and therefore have important implications for understanding the neuropathologic substrate of the disease from disrupted network organization perspective.     

Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study

Background

Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.

Methods

We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.

Results

The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.

Conclusions

ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.     

The Glutathione S-Transferase P1 341C>T Polymorphism and Cancer Risk: A Meta-Analysis of 28 Case-Control Studies

Background

GSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted.

Methodology/Principal Findings

The relevant studies were identified through searching of PubMed, Embase, ISI Web of Knowledge and China National Knowledge Infrastructure in August 2012, and selected based on the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize the association of GSTP1 341C>T polymorphism with cancer susceptibility. Stratified analyses were employed to identify the source of heterogeneity. Publication bias was evaluated as well as sensitivity analysis. Based on 28 case-control studies with 13249 cases and 16798 controls, the pooled results indicated that the variant genotypes significantly increased the risk of cancer in homozygote comparison (TT versus CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, P _het. = 0.575), and recessive model (TT versus CT/CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, P _het. = 0.562). This was confirmed when stratified analyses were conducted according to ethnicity, source of control, matched control, quality score and cancer types. Moreover, significantly increased risk of cancer was also found in lung cancer (heterozygote comparison and dominant model). The stability of these observations was confirmed by a sensitivity analysis. Begger''s funnel plot and Egger''s test did not reveal any publication bias.

Conclusions/Significance

This meta-analysis suggests that the GSTP1 341C>T polymorphism may contribute to genetic susceptibility to cancer, especially to lung cancer, and in Asian population. Nevertheless, additional well-designed studies focusing on different ethnicity and cancer types are needed to provide a more exact and comprehensive conclusion.     

Investigation of MTHFR C677T Gene Polymorphism, Biochemical and Clinical Parameters in Turkish Migraine Patients: Association with Allodynia and Fatigue

We investigated whether there is any relationship between biochemical and clinical parameters of migraine and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism, associated with the migraine subtypes, symptoms, and gender. A total of 150 migraine patients with and without aura (MA and MO) and 107 non-sufferers were included in the study. Biochemical and clinical parameters were measured and genetic analysis was performed. The MTFHR C677T genotype was significantly higher in the migraine group (p = 0.000). The CT genotype frequency of individuals with a family history of migraine was significantly higher (p = 0.025). This genotype frequency was higher in patients who suffer from compression, allodynia, fatigue, and sleeplessness (p = 0.027, 0.023, 0.006, and 0.05, respectively). Homocysteine and total cholesterol levels were significantly higher in the migraine group than the control group (p = 0.007 and 0.010, respectively). However, the other biochemical and clinical parameters did not differ from each other (p > 0.05), with only attack frequency being significantly higher in the MO group (p = 0.005). While the folate and HDL levels were significantly higher in females (p = 0.001 and 0.000, respectively), the homocysteine and triglyceride levels were significantly higher in males (p = 0.000 for each one). BMIs were significantly lower in the control than the migraine group (p = 0.021); however, an association between the C677T variant and BMI was not found (p = 0.787) in the migraine group. An association between the MTHFR C667T polymorphism and migraine susceptibility was found. Additional studies including genetic, clinic, and biochemical parameters should be conducted to better understand the disease.     

The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease

PurposeThe changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant.MethodsWe used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity.ResultsThe mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the non-PTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46–0.94).ConclusionParathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism.     

Association between Methylenetetrahydrofolate Reductase C677T Polymorphism and Susceptibility to Cervical Cancer: A Meta-Analysis

Background

To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, and Web of Science databases, we identified outcome data from all articles estimating the association between MTHFR polymorphism and cervical cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 12 studies with 2,924 cases (331 cervical intraepithelial neoplasia (CIN) I, 742 CIN II/III, 1851 invasive cervical cancer) and 2,581 controls were identified. There was no significant association between MTHFR C677T polymorphism and CIN I risk (T vs. C, OR = 1.10, 95% CI = 0.92–1.31; TT vs. CC, OR = 1.14, 95% CI = 0.78–1.68; TT+CT vs. CC, OR = 1.22, 95% CI = 0.94–1.58; TT vs. CT+CC, OR = 0.99, 95% CI = 0.70–1.40). For the CIN II/III, lack of an association was also found (T vs. C, OR = 1.08, 95% CI = 0.95–1.23; TT vs. CC, OR = 1.15, 95% CI = 0.87–1.52; TT+CT vs. CC, OR = 1.13, 95% CI = 0.94–1.35; TT vs. CT+CC, OR = 1.07, 95% CI = 0.83–1.38). The T allele had significant association to susceptibility of invasive cervical cancer in recessive model (TT vs. CT+CC, OR = 1.23, 95% CI = 1.02–1.49). On subgroup analysis by ethnicity, similarly significant differences in T vs. C, TT vs. CC, and recessive model were found in Asians.

Conclusion

The present meta-analysis suggested that MTHFR C677T polymorphism were to substantially contribute to invasive cervical cancer in recessive model.     

Prevalence of MTHFR C677T Single Nucleotide Polymorphism in Genetically Isolated Populations in Jordan

Methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism is a major inherited risk factor of venous thromboembolism. We sought to determine its prevalence in genetically isolated populations of Chechens and Circassians in Jordan. The MTHFR C677T mutation was analyzed from blood samples taken from 120 random unrelated Chechens and 72 Circassians. The prevalence of the MTHFR mutation in the Chechen population was 27.5% (allele frequency 15%); the prevalence among the Circassians was 50% (allele frequency 29.2%). The prevalence in the Chechen population is similar to that in Jordan and other world populations, but it is higher in the Circassian population. This study will contribute to understanding the interaction between genetic and environmental risk factors underlying thrombosis and will be useful in deciding which genetic variants should be tested in a clinical genetic testing service.     

Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis

Background

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies.

Methodology/Principal Findings

We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included ‘Pubmed’, ‘Ovid’ and ‘Google Scholar’. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility.

Conclusions/Significance

677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.     

Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies

Background

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.

Aim

A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.

Methods

PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment.

Results

Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09–1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13–1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10–1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13–1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60–0.94, p = 0.01).

Conclusion

The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.     

Progressive Rise in Red Blood Cell Distribution Width Predicts Mortality and Cardiovascular Events in End-Stage Renal Disease Patients

Red blood cell distribution width (RDW) is a robust marker of adverse clinical outcomes in various populations. However, the clinical significance of a progressive rise in RDW is undetermined in end-stage renal disease (ESRD) patients. The purpose of this study was to determine the prognostic importance of a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis patients were retrospectively analyzed. Temporal changes in RDW during 12 months after dialysis initiation were assessed by calculating the coefficients by linear regression. Patients were divided into two groups: an RDW-decreased group who had negative coefficient values (n = 177) and an RDW-increased group who had positive values (n = 149). The associations between rising RDW and mortality and cardiovascular (CV) events were investigated. During a median follow-up of 2.7 years (range, 1.0–7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events (18.4%) occurred. The event-free survival rate for the composite of end-points was lower in the RDW-increased group (P = 0.004). After categorizing patients according to baseline RDW, the event-free survival rate was lowest in patients with a baseline RDW >14.9% and increased RDW, and highest in patients with a baseline RDW ≤14.9% and decreased RDW (P = 0.02). In multivariate analysis, rising RDW was independently associated with the composite of end-points (hazard ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that a progressive rise in RDW independently predicted mortality and CV events in ESRD patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD patients.