Evaluation of the Relationship Between Dopamine Receptor D2 Gene TaqIA1 Polymorphism and Alcohol Dependence Risk.

Several studies are published, that investigated dopamine receptor 2 (DRD2) gene TaqIA polymorphism as a risk factor for alcohol dependence (AD) with positive and negative associations. To derive a more precise estimation of the relationship, a meta-analysis of case-control studies that examined the association between DRD2 gene Taq1A polymorphism and alcohol dependence was performed. Eligible articles were identified through a search of databases including PubMed, Science Direct, Springer link, and Google Scholar. The association between the DRD2 TaqIA polymorphism and AD susceptibility was conducted using odds ratios (ORs) and 95% confidence intervals (95% CIs) as association measures. A total of 69 studies with 9125 cases and 9123 healthy controls were included in the current meta-analysis. Results of the present analysis showed significant association between DRD2 TaqIA polymorphism and AD risk using five genetic modes (allele contrast model-OR 1.22, 95% CI 1.13-1.32, p < 0.0001; homozygote model-OR 1.35, 95%CI 1.18-1.55; p ≤ 0.0001; dominant model-OR 1.29; 95% CI 1.20-1.39; p < 0.0001; recessive model-OR 1.21; 95% CI 1.08-1.36; p = 0.0006). There was no significant association found in subgroup analysis, TaqIA polymorphism was not significantly associated with AD risk in the Asian population under all genetic models, but in the Caucasian population, TaqIA polymorphism was significantly associated with AD risk. Overall, results support the hypothesis that DRD2 Taq1A polymorphism plays a role in alcohol dependence.

Myosin IIA suppresses glioblastoma development in a mechanically sensitive manner.

The ability of glioblastoma to disperse through the brain contributes to its lethality, and blocking this behavior has been an appealing therapeutic approach. Although a number of proinvasive signaling pathways are active in glioblastoma, many are redundant, so targeting one can be overcome by activating another. However, these pathways converge on nonredundant components of the cytoskeleton, and we have shown that inhibiting one of these-the myosin II family of cytoskeletal motors-blocks glioblastoma invasion even with simultaneous activation of multiple upstream promigratory pathways. Myosin IIA and IIB are the most prevalent isoforms of myosin II in glioblastoma, and we now show that codeleting these myosins markedly impairs tumorigenesis and significantly prolongs survival in a rodent model of this disease. However, while targeting just myosin IIA also impairs tumor invasion, it surprisingly increases tumor proliferation in a manner that depends on environmental mechanics. On soft surfaces myosin IIA deletion enhances ERK1/2 activity, while on stiff surfaces it enhances the activity of NFκB, not only in glioblastoma but in triple-negative breast carcinoma and normal keratinocytes as well. We conclude myosin IIA suppresses tumorigenesis in at least two ways that are modulated by the mechanics of the tumor and its stroma. Our results also suggest that inhibiting tumor invasion can enhance tumor proliferation and that effective therapy requires targeting cellular components that drive both proliferation and invasion simultaneously.

Relation Between Methylenetetrahydrofolate Reductase Polymorphisms (C677T and A1298C) and Migraine Susceptibility.

Migraine is a neurological disorder which impairs the patient's quality of life. Several association studies investigating the association between MTHFR gene C677T and A1298C polymorphisms and susceptibility to migraine were published. But the results were conflicting, so authors performed a meta-analysis of published case control studies to find out the exact association between MTHFR polymorphism and migraine susceptibility. Four databases were searched for suitable studies up to December, 2018. Odds ratios (OR) with 95% confidence intervals (CI) was calculated adopting additive, homozygote, co-dominant, dominant, and recessive genetic models. Results of MTHFR C677T polymorphism studies meta-analysis showed significant association with migraine risk using allele contrast, homozygote, dominant and recessive genetic models (T vs. C: OR = 1.18, 95% CI = 1.00-1.26, p = 0.05; TT vs. CC: OR = 1.24, 95% CI = 1.0-1.5, p = 0.04; CT vs. CC: OR = 1.08, 95% CI = 0.97-1.07, p = 0.25; TT + CT vs. CC: OR = 1.15, 95% CI = 1.0-1.29, p = 0.04; TT vs. CT + CC: OR = 1.97, 95% CI = 1.28-3.42, p = 0.002). However, results of MTHFR A1298 polymorphism studies meta-analysis did not show any association with migraine. Subgroup analysis based on ethnicity and migraine types i.e. migraine with aura (MA) and without aura (MO) were also performed. Results of present meta-analysis indicate overall association between MTHFR C677T polymorphism with migraine in total 24 studies, in Asian population and in MA cases but did not show any association with Caucasian population and MO cases.

The association of ABO blood group with the asymptomatic COVID-19 cases in India.

The COVID-19 pandemic resulted in multiple waves of infection worldwide. The large variations in case fatality rate among different geographical regions suggest that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was demonstrated that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies among 509 individuals, collected from three major districts of Eastern Uttar Pradesh region of India. Interestingly, we found neutralising antibodies in a significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). We further estimated that people with blood group AB are at comparatively higher risk of infection than other blood groups. Thus, among the asymptomatic SARS-CoV-2 recovered people blood group AB has highest, whilst individuals with blood group O has lowest risk of infection.

Distribution of Methionine Synthase Reductase (MTRR) Gene A66G Polymorphism in Indian Population.

Methionine synthase reductase (MTRR) is an important enzyme of the folate/homocysteine pathway. It is responsible for regulation of methionine enzyme by reductive methylation. A common variant A66G is reported in the FMN-binding domain of the MTRR gene, which leads to substitution of isoleucine by methionine (I22M) in MTRR enzyme with reduced activity. Reduced catalytic activity of enzyme leads to high homocysteine concentration in blood and increases risk for numerous diseases. The frequency of A66G polymorphism varies in different ethnic groups. The present study has been designed to evaluate the frequency of MTRR A66G gene polymorphism in the Eastern UP population by PCR-RFLP method. Along with this we also performed a meta-analysis to evaluate the global prevalence of this polymorphism. Databases were screened to identified the eligible studies. The prevalence of the G allele and GG genotype was determined by the use of prevalence proportion with 95% CI. Open meta-analyst software was used for the meta-analysis. Total 1000 blood samples were analyzed, the frequencies of A and G alleles were 0.35 and 0.65 respectively. Meta-analysis results revealed that the prevalence of G allele and GG genotype were 49.4% (95% CI 40.6-58.1, p ≤ 0.001) and 24.3% (95% CI 17.8-30.9, p ≤ 0.001) respectively. In sub-group meta-analysis, the lowest frequency of G allele was found in South America (32.7%; 95% CI 14.1-51.3, p ≤ 0.001), and highest in Asia (56.4%; 95% CI 39.5-73.3, p ≤ 0.001). The results of the meta-analysis showed that the Asian population has the highest frequency of G allele and highest frequency of the GG genotype was found in the European population.

Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Susceptibility to Alcohol Dependence.

Catechol-O-methyl transferase (COMT) enzyme catalyzes the metabolism of dopamine and other catechols in the brain. Several articles investigated catechol-O-methyltransferase (COMT) Val158Met polymorphism as risk factor for alcohol dependence (AD) but the results were inconclusive. The aim of present meta-analysis was to evaluate the association of Val158Met (COMT) polymorphism with AD. Authors performed keyword search of the 4 electronic databases-Pubmed, Google Scholar, Springer Link and Science Direct databases up to December 31, 2019. Total eighteen studies that investigated the association of Val158Met polymorphism with AD were retrieved. The pooled results from the meta-analysis (2278 AD cases and 3717 healthy controls) did not show association with AD using all 5 genetic models (allele contrast model: OR = 1.02, 95% CI = 0.90-1.14, p = 0.03; homozygote model: OR = 1.06, 95% CI = 0.81-1.38, p = 0.69; dominant model: OR = 0.99, 95% CI = 0.85-1.14, p = 0.87; co-dominant model: OR = 0.97, 95% CI = 0.86-1.11, p = 0.71; recessive model: OR = 1.05;95% CI = 0.85-1.29, p = 0.61). Results of subgroup analysis showed that Val158Met is not risk for AD in Asian and Caucasian population. In conclusion, COMT Val158Met is not a risk factor for alcohol dependence.

Catechol-O-methyltransferase gene Val158Met polymorphism and obsessive compulsive disorder susceptibility: a meta-analysis.

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that affects approximately 1-3% of the general population. It is characterized by disabling obsessions (intrusive unwanted thoughts) and/or compulsions (ritualized repetitive behaviors). Catechol-O-methyltransferase (COMT) enzyme has an important role in inactivation of dopamine and higher dopamine levels may be implicated in OCD, hence COMT gene is a suitable candidate for OCD. Several case-control studies have evaluated the role of COMT Val 158Met (rs4680;472G- > A) polymorphism as a risk factor for OCD but the results remained inconclusive, hence present meta-analysis was designed to find out correct assessment. All studies that investigated the association of COMT gene Val158Met polymorphism with OCD risk, were considered in the present meta-analysis. Statistical analysis was performed with the software program MetaAnalyst. In the current meta-analysis, 14 case-control studies with 1435 OCD cases and 2753 healthy controls were included. The results indicated significant association between COMT Val158Met polymorphism and OCD risk using allele contrast, homozygote and dominant models (ORA vs G = 1.14; 95% CI = 1.02-1.27; p = 0.01; ORAAvs.GG = 1.33; 95% CI = 1.09-1.62, p = 0.004; ORAA + AGvs.GG = 1.14; 95% CI = 1.0-1.32; p = 0.04). In subgroup analysis based on case gender, meta-analysis of male cases showed significant association using all five genetic models (ORAAvsGG = 1.99; 95%CI = 1.42-2.59; p = <0.001; ORAA + AGvs.GG = 1.59; 95% CI = 1.20-2.10; p = 0.001), but did not show any association between COMT Val 158Met polymorphism and OCD risk in females. In conclusion, results of present meta-analysis supports that the COMT Val158Met polymorphism is a risk factor for OCD especially for males.

Evaluation of COMT Gene rs4680 Polymorphism as a Risk Factor for Endometrial Cancer.

Catechol-O-methyletransferase (COMT) enzyme is involved in the inactivation of catecholamine and catechol estrogens. Catechol estrogens have carcinogenic potential and DNA damaging ability. Several studies investigated COMT Val158Met polymorphism as risk factor for endometrial cancer but the results were inconclusive. Hence the objective of present study was to find out exact association between COMT gene Val158Met polymorphism and endometrial cancer by a meta-analysis. Pubmed, Google Scholar, Springer Link and Science Direct databases were searched for case-control articles which investigated COMT Val158Met polymorphism in endometrial cancer cases. All statistical analysis was performed using MetaAnalyst and Mix programs. The results of meta-analysis suggested that there were no association between COMT Val158Met polymorphism and endometrial cancer risk (allele contrast model-ORA vs. G = 0.97, 95% CI = 0.86-1.10, p = 0.67; co-dominant model-ORAG vs. GG = 0.91, 95% CI = 0.77-1.06, p = 0.23; homozygote model-ORAA vs. GG = 1.01, 95% CI = 0.84-1.19, p = 0.29; dominant model-ORAA+AG vs. GG = 0.93, 95% CI = 0.77-1.11, p = 0.43; recessive model-ORAA vs. AG+GG = 1.02, 95% CI = 0.89-1.20, p = 0.62). Publication bias was absent. Subgroup analysis based on source of controls was also performed. In conclusion, results of present meta-analysis showed no association between COMT Val158Met polymorphism and susceptibility to endometrial cancer.

Myosin IIA Heavy Chain Phosphorylation Mediates Adhesion Maturation and Protrusion in Three Dimensions.

Non-muscle myosin II (NMII) is a conserved force-producing cytoskeletal enzyme with important but poorly understood roles in cell migration. To investigate myosin heavy chain (MHC) phosphorylation roles in 3D migration, we expressed GFP-tagged NMIIA wild-type or mutant constructs in cells depleted of endogenous NMIIA protein. We find that individual mutation or double mutation of Ser-1916 or Ser-1943 to alanine potently blocks recruitment of GFP-NM-IIA filaments to leading edge protrusions in 2D, and this in turn blocks maturation of anterior focal adhesions. When placed in 3D collagen gels, cells expressing wild-type GFP MHC-IIA behave like parental cells, displaying robust and active formation and retraction of protrusions. However, cells depleted of NMIIA or cells expressing the mutant GFP MHC-IIA display severe defects in invasion and in stabilizing protrusions in 3D. These studies reveal an NMIIA-specific role in 3D invasion that requires competence for NMIIA phosphorylation at Ser-1916 and Ser-1943. In sum, these results demonstrate a critical and previously unrecognized role for NMIIA phosphorylation in 3D invasion.

"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H): quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Authors conducted a meta-analysis to investigate association between C609T polymorphism and DT cancer risk. Eligible studies were extracted from the databases of PubMed, Google Scholar, Science Direct, and Springer Link. All retrieved articles were evaluated. All statistical analyses were performed using Open Meta-Analyst and MIX1.7 programs. A total of 34 studies including 12,043 DT cancer cases and 15,209 healthy controls were included in the present meta- analysis. Results of meta-analysis revealed a significant association between NQO1 C609T polymorphism and DT cancer risk adopting all 5 genetic models (T vs. C: OR = 1.21, 95% CI = 1.11-1.31, p < 0.001; TT vs. CC: OR = 1.48, 95% CI = 1.22-1.79, p < 0.001; TT + CT vs. CC: OR = 1.23, 95% CI = 1.12-1.35, p < 0.001; TT vs. CT + CC: OR = 1.36, 95% CI = 1.15-1.60, p < 0.001; CT vs. CC: OR = 1.16, 95% CI = 1.07-1.27, p < 0.001). In the stratified analysis based on cancer types, significant associations were observed between NQO1 C609T polymorphism and GC (OR = 1.38, 95% CI = 1.11-1.72, p = 0.003) and CRC (OR = 1.18, 95% CI = 1.06-1.30, p = 0.001), but not with EC (OR = 1.16, 95% CI = 0.99-1.35, p = 0.06). Furthermore, stratified analysis based on ethnicity indicated that there was a significant association between NQO1 C609T polymorphism and DT cancer risk in the Asian (TT vs. CC: OR = 1.55, 95% CI = 1.21-2.00, p ≤ 0.001) as well as in Caucasian populations (TT vs. CC: OR = 1.34, 95% CI = 1.04-1.73, p = 0.02). In conclusion, the results of meta-analysis suggested that the NQO1 C609T polymorphism is a risk factor for DT cancers, including GC and CRC.

Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism was reported as risk factor for multiple diseases due to its role in conversion of homocysteine to methionine. The aim of the present meta-analysis was to find out the validity of association of C677T polymorphism with epilepsy susceptibility. METHODS: Pubmed, Science Direct, Springer Link and Google Scholar, databases were searched for relevant studies up to January, 31, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed using five genetic models. All statistical analysis was done by MetaAnalyst and Mix programs. RESULTS: Except recessive model, significant association was found between MTHFR C677T polymorphism and epilepsy risk in other four genetic models (T vs C: OR = 1.29, 95% CI = 1.08-1.52, p = 0.004; TT vs CC: OR = 1.48, 95% CI = 1.19-1.82, p = 0.0003; TT + CT vs CC: OR = 1.20, 95% CI = 1.05-1.38, p = 0.008; TT vs CT + CC: OR = 1.35, 95% CI = 1.11-1.62, p = 0.002). Similarly, in the subgroup analysis based on ethnicity, significant association was found in Asian (T vs C: OR = 1.85; 95% CI = 1.15-2.99; p = 0.03) and Caucasian populations (TT vs CC: OR = 1.38; 95% CI = 1.10-1.1.73; p = 0.005). No evidence of heterogeneity and publication bias was detected in present meta-analysis. CONCLUSION: In conclusion, results of present meta-analysis suggested that 677T allele of MTHFR is significantly increases the epilepsy susceptibility.

Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P).

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigentic process of DNA methylation. It has been reported that abnormal DNA methylation contributes to the pathogenesis of congenital anomalies. There were many published case control studies assessing the associations of MTHFR C677T polymorphism with risks of nosyndromic cleft lip with and without palate (nsCL/P), but with inconsistent results. To derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified by search of databases including PubMed, Science Direct, Google Scholar and Springer Link up to December, 2015. Finally, a total of 22 studies with 3724 nsCL/P cases and 5275 controls were included in the present meta-analysis. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association. Subgroup analysis based on ethnicity was also performed. All statistical analyses were done by MIX program. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased nsCL/P risk in overall population using four genetic models except homozygote model (for T vs. C: OR = 1.24, 95% CI = 1.1-1.4; for TT + CT vs. CC: OR = 1.29, 95% CI = 1.04-1.59; for CT vs. CC: OR = 1.26, 95% CI = 0.98-1.63; for TT vs. CC: OR = 1.02, 95% CI = 0.74-1.4; for TT vs. CT + CC: OR = 1.36, 95% CI = 1.05-1.74). In conclusion, results of present meta-analysis suggested that MTHFR C677T polymorphism is significantly associated with nonsyndromic orofacial cleft.

Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.

BACKGROUND & OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. METHODS: PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. RESULTS: The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). INTERPRETATION & CONCLUSIONS: MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.

Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Male Infertility in Asian Population.

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of folate pathway and required for DNA synthesis and methylation. MTHFE C677T polymorphisms is reported as risk factors for various diseases and disorders like birth defects, metabolic, neurological, psychiatric disorders, and cancers. Several studies have investigated association between the MTHFR C677T polymorphism and male infertility. To assess the risk associated with MTHFR C677T polymorphism in Asian population, a meta-analysis was performed. Included articles were collected from the following electronic databases: PubMed, Google Scholar, and Science direct up to March 2015. Risk was estimated as pooled odds ratios (ORs) with confidence intervals (CIs) for assessment. Seventeen case-control studies involving 4392 breast infertile males and 3667 fertile males were found suitable for the inclusion in the present meta-analysis. Results showed that the C677T polymorphism was significantly associated with male infertility in Asian population using all the five genetic models (ORT vs. C (allele contrast model) = 1.86, 95% CI 1.7-2.0; ORTT vs. CC (homozygote model) = 1.96, 95% CI 1.67-2.30; ORCT vs. CC (co-dominant model) = 1.40, 95% CI 1.18-1.62; ORTT+CT vs. CC (dominant model) = 1.53, 95% CI 1.30-1.77; ORTT vs. CT+CC (recessive model) = 1.67, 95% CI 1.44-1.92). In conclusion, results of present meta-analysis strongly supported an association between C677T polymorphism and male infertility in Asians.

Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate pathway. Several polymorphisms were reported in MTHFR gene but C677T polymorphism is most studied and it has been reported to be risk factor for several diseases/disorders. The present study was designed to explore the frequency of MTHFR C677T polymorphism in North Indian healthy population. In addition to this a meta-analysis of published articles was also performed to estimate the global prevalence of MTHFR C677T polymorphism. A total of 1000 unrelated healthy subjects were selected for MTHFR C677T polymorphism analysis. Different databases were searched for eligible articles. Prevalence proportion with 95 % CI was used to determine global prevalence of T allele and TT genotype. Meta-analysis was performed by Open meta-analyst. In 1000 blood samples analyzed, the frequency of T allele and TT genotype was 11 and 1 % respectively. Results of the meta-analysis showed that the global prevalence of T allele and TT genotype were 24.0 % (95 % CI 21.7-26.5) and 7.7 % (95 % CI 6.5-8.9) respectively. In sub-group meta-analysis, the lowest frequency of T allele was found in Africans (10.3 %; 95 % CI 3.8-16.8), and highest in Europeans (34.1 %; 95 % CI 31.9-36.3). The frequency of T allele in the North India is 11 %. The results of the meta-analysis showed that the frequency of the T allele and the TT genotype of C677T is highest in the Caucasian population.

Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.

Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to Alzheimers disease (AD) was controversial in previous studies. The present meta-analysis was designed to investigate the association of MTHFR C677T polymorphism with AD. Nine studies were identified by search of PubMed, Google Scholar, Elsevier, Springer Link databases, up to January 2013. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effects model or random effects model. All statistical analysis was done by Mix version 1.7. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C: OR 1.29, 95 % CI 1.15-1.44, p < 0.0001; for TT + CT vs CC: OR 1.38, 95 % CI 1.16-1.364, p = 0.0002; for TT vs CC: OR 1.60, 95 % CI 1.25-2.04, p = 0.0001; for CT vs CC: OR 1.28, 95 % CI 1.1-1.53, p < 0.008; for TT vs CT + CC: OR 1.37, 95 % CI 1.12-1.67, p = 0.002). Results from present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD in Asian population.

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis.

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case-control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09-1.68, p = 0.009; for TT + CT vs. CC: OR 1.44, 95 % CI 1.14-1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07-1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI 1.23.2.6, p = 0.007; for TT vs. CT + CC: OR 1.61, 95 % CI 1.02-2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention.

"Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis".

Epidemiological studies have evaluated the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms and risk of neural tube defects (NTDs) in offspring. However, the results from the published studies on the association between these three polymorphisms and NTD risk are conflicting. To derive a clearer picture of association between these three maternal polymorphisms and risk of NTD, we performed meta-analysis. A comprehensive search was conducted to identify all case-control studies of maternal MTHFR and MTRR polymorphisms and NTD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk. However, in stratified analysis by geographical regions, we found that the maternal C677T polymorphism was significantly associated with the risk of NTD in Asian (OR(TvsC) = 1.43; 95% CI: 1.05-1.94), European (OR(TvsC) = 1.13; 95% CI: 1.04-1.24) and American (OR(TvsC) = 1.26; 95% CI: 1.13-1.41) populations. In conclusion, present meta-analysis supports that the maternal MTHFR C677T and MTRR A66G are polymorphisms contributory to risk for NTD.

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India.

BACKGROUND: Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not. OBJECTIVE: We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864). CONCLUSION: Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.