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 (OR_{T vs. C} (allele contrast model) = 1.86, 95% CI 1.7–2.0; OR_{TT vs. CC} (homozygote model) = 1.96, 95% CI 1.67–2.30; OR_{CT vs. CC} (co-dominant model) = 1.40, 95% CI 1.18–1.62; OR_{TT+CT vs. CC} (dominant model) = 1.53, 95% CI 1.30–1.77; OR_{TT 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.     

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.     

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.     

C677T MTHFR Gene Polymorphism is Contributing Factor in Development of Renal Impairment in Young Hypertensive Patients

Homocysteine concentration affected by the activities of the enzymes methylene tetra-hyrdofolate reductase (MTHFR). Polymorphisms in MTHFR gene associated with an impairment of MTHFR activity. Hyperhomocysteinemia is a result of single nucleotide polymorphisms (SNPs) in MTHFR 677 C>T that can cause homocysteine levels in the blood to increase. The purpose of this study is to investigate the relationships between MTHFR C677T (rs1801133) gene polymorphism, changes in homocysteine concentrations and progress of renal impairment in young adult hypertensive patients. Two hundred young hypertensive patients (age 21–24 years) were involved in this study; they were classified into patients with and without renal impairment in addition to 200 age and sex matched healthy controls. All participants were submitted to laboratory investigations as assay of MTHFR gene polymorphism C677T (rs1801133) by PCR/RFLP, determination of lipid profile, homocysteine and folic acid concentrations in addition to urinary albumin creatinine ratio (UACR). The levels of both homocysteine and UACR in the TT genotype patients were higher than those in the CC genotype group. Individuals who carry the T allele were more risky to hypertension and progress to early renal impairment in young age compared with those carrying the C allele [OR 2.02 (1.33–3.08), P < 0.001]. Genetic variants of C677T MTHFR gene and hyperhomocysteinemia may be responsible for rapid progress of renal impairment in Egyptian young age hypertensive patients. TT genotype or T allele may be considered as a predisposing factor for both elevated Hcy levels and the development of renal impairment. This study believed that lowering of homocysteine level can reduce renal impairment of hypertensive patients.     

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.     

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction–restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects (P = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.     

Polymorphism (C677T) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene: A preliminary study on north Indian men

An elevated level of plasma homocysteine, sulfur containing amino acid generated through demethylation of methionine has been widely accepted as a risk factor for cardiovascular disease (CVD). The increase can result from genetic and/or nutrient related disturbances in the remethylation or transsulfuration pathways for homocysteine metabolism. A common mutation (C677T) in the gene encoding for the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) or deficiency of the B vitamins namely folic acid, B₁₂, B₆ can lead to hyperhomocysteinemia. In the present study, we have investigated the incidence of the (C677T) MTHFR polymorphism in the North Indian males. 141 angiographically proven coronary artery disease (CAD) patients and 55 age and sex matched healthy volunteers were examined for the association between MTHFR gene polymorphism and CAD. The MTHFR genotyping was performed using polymerase chain reaction (PCR) followed by restriction-isotyping with Hinf 1 endonuclease. A trend for higher ‘T’ allele frequency (0.19) was observed in patients than in controls (0.16). However no significant association was found between C677T mutation and CAD severity. The lack of statistical significance could be due to the small sample size studied. Hence a larger study including various ethnic groups is warranted.     

Angiotensin Converting Enzyme Gene Polymorphism and its Association with Hypertension in South Indian Population

Hypertension, a well known risk factor for various cardiovascular, peripheral vascular and renal events is an important public health challenge. Renin angiotensin system (RAS) being the most vital pathogenic mechanism of hypertension is mediated by a key component; the angiotensin converting enzyme (ACE). The present study was aimed to know the relationship of ACE gene polymorphism and the possible risk of development of hypertension in south Indian population. The study included 101 clinically diagnosed hypertensive patients without any associated disease condition and 81 age and sex matched apparently healthy controls. Genotyping was performed using a polymerase chain reaction, (PCR) amplification of the intron 16 fragment harboring the 287 bp Alu repeat sequence. Three possible genotypes D/D, I/I homozygous and I/D heterozygous were analyzed where the D/D genotypes corresponds to higher ACE levels (D-Deletion, I-Insertion). The PCR products were separated on 2 % agarose gel. Statistical analysis was performed using SPSS.15 software program. We found a significance in frequency of D/D genotype in the hypertensive patients compared to the control group (p = 0.0005, odd’s ratio = 4.157). This suggested that ACE (D/D) genotypes are more prone for the development of hypertension. This is relatively a pilot study; but nevertheless may assist in identifying the pathophysiological cause of hypertension.     

Association of the 12669G&gt;A Apolipoprotein B Gene Polymorphism with Apo-B Serum Level and Lipid Profile in Patients with Coronary Artery Disease Comparing with Individuals Without Coronary Artery Disease in Zanjan Population of Iran

Atherosclerosis is a pathologic disorder which has an important role in the occurrence of coronary heart disease. It is determined as a focal, inflammatory proliferative response to several types of endothelial damage. Apolipoprotein B which is a requirement in the sustenance of cholesterol homeostasis, and is the major protein component of low density lipoprotein, characterized by multitude polymorphic sites, one of which (12669G>A) is related to the levels of serum lipid profiles, coronary artery disease and/or myocardial infarction. One Common polymorphism which is more important in this process is 12669G>A that is appraised in this research. We recruited 80 patients from the Mousavi hospital, Zanjan, Iran, diagnosed with coronary artery disease by the clinician on the basis of clinical symptoms, echocardiogram result, and angiography. Seventy-seven healthy individuals without any evident symptoms of Coronary stenosis and any past history of the disease were taken as controls from the general population. We carried out PCR using specific primers. Then, we digested PCR product by RFLP. Lipid parameters by biochemical methods and Apolipoprotein B serum level by immunoturbidometry method were done. Genotype frequencies for 12669G>A polymorphism were determined: 55 % R+R+, 45 % R+R? in case group, and 55.8 R+R+, 44.2 % R+R? in controls. The R?R? genotype was not seen. There was no significant relationship between this polymorphism and the risk of Coronary stenosis (P = 0.6). In the present study, higher plasma levels of cholesterol and low density lipoproteins in the subjects with R+R? genotype were found while there was no association between this polymorphism and coronary stenosis with ≥50 % in the Zanjan population.     

Prevalence of Factor V Leiden-G1691A and MTHFR-C677T Thrombosis Gene Modifier in Iron Deficiency Anemia: A Pathophysiological Effect in Indian Isolates

Normal iron levels are required to prevent thrombocytosis by inhibiting thrombopoiesis. Thrombocytosis is usually associated with a mild iron deficiency and is the result of a lack of inhibition of thrombopoiesis. Study participants were 430 iron deficiency anemia (IDA) patients. Ten (10) mL of venous blood were collected for the subjects. Ferritin analysis was done by ELISA method while Hemogram analysis was done by auto-analyzer. Factor V Leiden, PRTG20210A, and MTHFR C677T genotype analysis was performed by PCR–RFLP method. Among the patients, 9 were heterozygous (G>A) and 2 were homozygous (A>A) carrier of FV Leiden; while 20 were heterozygous (C>T) and 3 were homozygous (T>T) for MTHFR polymorphism. None of the patient was identified with PT mutation. Patients with thrombosis gene marker had lower hemoglobin, mean corpuscular volume, mean corpuscular haemoglobin levels, and mean corpuscular hemoglobin concentration than patients without thrombosis gene marker. Serum ferritin was elevated in subject with the absence of thrombosis gene markers. Our data suggest a high impact of inherited hypercoagulability risk factors in the pathogenesis of IDA and its complications.     

Impact of CCL2 and Its Receptor CCR2 Gene Polymorphism in North Indian Population: A Comparative Study in Different Ethnic Groups Worldwide

Chemokine are small, inducible pro-inflammatory cytokines involved in many biological processes, such as migration of leukocytes, atherosclerosis, angiogenesis, tumor growth, and metastasis. Chemokine are also known to influence tumor cell’s activity. Specifically, tumor cells express chemokine receptors in a non random manner suggesting a role of chemokine in metastatic destination of tumor cells. The present study was conducted to determine distribution of (Chemokine receptor 2) CCR2 V64I, Chemokine ligand 2 CCL2 I/D, and CCL2 2518 A>G gene polymorphisms in North Indian population and compare with different populations globally. Polymerase chain reaction (PCR)-based analysis was conducted in 200 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type (GG) of CCR2 V64I G>A were 63 % G; CCL2 I/D 42 % II; CCL2 2518 A>G 40.5 % A. The minor variant allele frequency in our population was as follows: 19.5 % for CCR2 V64I, 35.5 % for CCL2 I/D, 35.3 % for CCL2 2518 A>G. We further compared frequency distribution for these genes with various published studies in different ethnicity. Our results suggested that frequency in chemokine genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of human exposed to environmental carcinogens and cancer predisposition in different ethnic groups. Thus, they signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.     

舟山渔民心脑血管病危险因素水平的变化趋势

为观察舟山渔民心脑血管病危险因素水平的变化趋势,对该地区的渔民在１９９４年和１９９８年前后二次进行了有关心脑血管病危险因素水平的抽样调查,测量了该人群的收缩压（ＳＢＰ）、舒张压（ＤＢＰ）、总胆固醇（ＴＣ）、高密度脂蛋白－胆固醇（ＨＤＬ－Ｃ）、空腹血糖（ＦＢＳ）,体重指数（ＢＭＩ）以及人群中高血清总胆固醇现患率,低ＨＤＬ－Ｃ现患率和高血压患病率及吸烟率的状况。比较结果显示：男性ＳＢＰ,ＤＢＰ,ＴＣ,     

Genetic Variant XRCC1 rs1799782 (C194T) and Risk of Cancer Susceptibility in Indian Population: A Meta-analysis of Case–Control Studies

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. Several studies have reported contradictory results for XRCC1 exon 6 C>T (rs1799782) gene polymorphism and cancer risk in Indian population has provided inconsistent results. Therefore, we have performed this meta-analysis to evaluate the relationship between XRCC1 exon 6 C>T gene polymorphism and risk of cancer by published studies. We searched PubMed and Google scholar web databases to cover all studies published on association between XRCC1 exon 6 C>T gene polymorphism and cancer risk. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. In order to derive a more precise estimation of the association, A total of 3197 confirmed cancer cases and 3819 controls were included from eligible seventeen case-controls studies. Results from overall pooled analysis demonstrated suggested that that variant allele (T vs. C: OR 1.301, 95% CI 1.003–1.688, p = 0.047) was associated with the risk of overall cancer. Other genetic models; heterozygous (TC vs. CC: OR 1.108, 95% CI 0.827–1.485, p = 0.491), homozygous (TT vs. CC: OR 1.479, 95% CI 0.877–2.493, p = 0.142), dominant (TT+TC vs. CC: OR 1.228, 95% CI 0.899–1.677, p = 0.196) and recessive (TT vs. TC+CC: OR 1.436, 95% CI 0.970–2.125, p = 0.071) did not reveal statistical association. Publication bias observation was also considered and none was detected during the analysis. The present meta-analysis suggested that the variant allele T of XRCC1 exon 6 gene polymorphism was associated with the risk of cancer. It is therefore pertinent to confirm this finding in a large sample size to divulge the mechanism of this polymorphism and cancer risk in Indian population.     

Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary Artery Disease in Asian Indians

Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in the recent years as a candidate gene for hypertension, cardiovascular diseases and type 2 diabetes. The aim of the present study was to investigate the association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian population. A total of 662 subjects (330 CAD patients and 332 healthy controls) were examined for association of ACE gene (I/D) polymorphism and environmental risk factors. The mean age of the CAD patients and control subjects was 60.53 ± 8.6 years and 56.55 ± 7.7 years, respectively (p = 0.000). Anthropometric and demographic data showed BMI values significantly higher among CAD patients and control subjects (26.98 ± 4.9 vs 24.04 ± 4.7, p = 0.000). We observed pronounced central obesity in both CAD patients and controls, even at the lowest BMI values (<23 kg/m²). Dyslipidemia was highly prevalent in CAD patients compared to control subjects. Genotypic data showed significantly higher frequency of DD genotype in CAD patients than that of control subjects (40 vs 28.3 %). No significant difference was observed in the distribution of ID genotypes between CAD patients and control subjects. Logistic regression analysis of data demonstrate that DD genotype was associated with 1.8 fold increased risk of development of CAD in Asian Indians (OR 1.8; 95 % CI 1.22–2.66; p = 0.003). The frequency of D allele was significantly higher in CAD patients (p = 0.001). No significant difference was observed in the clinical and biochemical characteristics of CAD patients and controls when the data was stratified according to the genotypes of ACE gene. In conclusion, DD genotype of ACE gene may be associated with increased risk of CAD in Asian Indian population.     

Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure,Glucose in Northern Indians

Glucocorticoids and its receptor are known to be involved in the dysregulation of hormone and lipid levels. Therefore, we evaluated the association of Bcl1 gene polymorphism of glucocorticoids receptor (GCR) gene variant with hormone and lipid levels in Northern Indians obese. A total of 435 obese and non-obese age matched subjects were included in the case–control study. Lipid and hormonal levels were estimated using standard protocols. Analysis of +646 C>G NR3C1 gene polymorphism was done using PCR–RFLP. The frequencies of GR Bcl1, C>G genotypes and alleles did not differ significantly (P > 0.05) between obese and non-obese. The +646 G allele carriers had higher waist to hip ratio, blood pressure, insulin and glucose levels than non-carriers in obese subjects while diastolic blood pressure and glucose in non-obese. The NR3C1, +646 C>G polymorphism did not associate with obesity. However, the GG genotype may modulate blood pressure, blood glucose and hormonal levels in northern Indians.     

Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has role in atherosclerotic plaque development as well as in thrombosis leading to myocardial infarction (MI). Present study was aimed to analyse the association of PECAM-1 Leu125Val gene polymorphism with MI in Indian population. Subjects included healthy individuals as control (N = 116) and MI patients (N = 100) divided into two groups; MI patients at presentation of the acute event (MI-Group-1, N = 46) and patients with recent event of MI stabilized with treatment 4.5 days from their symptoms (MI-Group-2, N = 54). The difference in the distribution of Leu125Val genotype frequencies of controls and patients did not reach statistical significance. However Leu allele frequency (0.57) was more associated with MI patients as compared to control (0.504). sPECAM-1 levels were significantly elevated in patients at acute event of MI (MI-Group-1) by 44.1% (P = 0.009) as compared to controls and by 95.2% (P = 0.001) as compared to stabilized MI patients (MI-Group-2).     

Correlation Between Intron 4 Polymorphism of the Endothelial Nitric Oxide Synthase Gene and Cardiovascular Risk with the Numbers of Circulating Endothelial Progenitor Cells in Healthy Subjects

In the present study, we investigated the relationship between an important 27 bp repeat polymorphism in intron 4 of eNOS and numbers of circulating EPCs in presence of cardiovascular disease (CVD) risk factors in a group of healthy human volunteers. The study comprised of 45 healthy subjects (30–50 years). These subjects had various degrees of CVD risk but no history of CVD. The repeat polymorphism of eNOS was detected by polymerase chain reaction and EPC levels were analyzed by flow cytometry. We observed a good association between the intronic 4 mutant a/b genotype and the combined Framingham risk factor score in our subjects (χ² = 3.2, P = 0.07). EPC numbers in subjects with mutant eNOS a/b genotype were also less than those observed in subjects with normal eNOS b/b genotype (P = 0.06). Interestingly, subjects with eNOS a/b genotype showed a significant inverse correlation between framingham risk score and EPC numbers (R = ?0.57, P < 0.05). The study suggests that the presence of CVD risk factors in subjects with eNOS intron 4 polymorphism results in reduced number of circulating EPCs, which may significantly predispose them to CVD and aberrant endothelial repair.     

C2C网上交易中感知风险与第三方支付担保服务使用

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